Biology subjects

Banerjee, M.

Publications and source records attributed to Banerjee, M..

At least 19 recordsLinked to original sources

bioRxiv2026

A Computational Framework for Understanding HCV Infection and Associated Lipid Dynamics

Hepatitis C virus (HCV) infection is strongly intertwined with host lipid metabolism and is frequently associated with hepatic steatosis, particularly in genotype-specific cases where lipid accumulation reflects direct viral effects rather than host metabolic comorbidities. Despite extensive clinical and experimental evidence, a quantitative framework capturing the bidirectional coupling between viral dynamics and lipid metabolism remains lacking. In this work, we develop a comprehensive mathematical model that integrates HCV infection dynamics with intracellular lipid regulation. The framework combines a reaction diffusion system for spatial viral spread with a coupled metabolic module describing lipid influx. Numerical simulations highlight the role of lipid feedback in shifting infection outcomes toward persistence and recurrent oscillations, demonstrating that lipid accumulation acts as a critical driver of viral amplification. The model also highlights the critical role of immune memory to study acute and chronic phase and successfully reproduces observed viral RNA trajectories. Overall, the framework provides mechanistic insights into HCV dynamics and offers a general modeling approach for studying virus metabolism interactions in liver disease.

cell biology↗

bioRxiv2026

Unravelling the role of a disordered chaperone in adaptation to environmental stress

Intrinsically disordered proteins (IDPs) lack a stable tertiary structure, which enables them to mediate flexible molecular interactions. As the biochemical functions of IDPs remain poorly understood, their physiological roles are largely unknown, particularly in photosynthetic organisms. Herein, Alr0806, a conserved salinity-induced cyanobacterial IDP, was characterized from the nitrogen-fixing cyanobacterium Anabaena. Instead of the full-length protein predicted in databases, experimental analysis indicated this organism to express a shorter form of the Alr0806 protein, which was attributed to the mis-annotation of the translational start codon. Purified Alr0806, a highly thermostable protein, exhibited characteristic properties of highly disordered proteins, including anomalous migration on SDS-PAGE. Alr0806 displayed disorder-to-order transitions with decreasing pH, indicating structural flexibility. Notably, Alr0806 leveraged structural plasticity to function as a chaperone and molecular shield, protecting proteins from aggregation. Furthermore, consistent with this function, Anabaena strains deficient in Alr0806 showed compromised growth and diminished photosynthesis under standard conditions of growth or in response to salt/heat stress. These findings establish Alr0806 as a key player in cyanobacterial physiology and provide insights into the physiological functions of IDPs in photosynthetic organisms. HighlightAlr0806, a conserved cyanobacterial stress-induced intrinsically disordered protein, exhibits structural plasticity and functions as a molecular chaperone to support growth, photosynthesis and environmental stress tolerance.

molecular biology↗

bioRxiv2026

Spatial pattern formation as a consequence of Protease Competition

Exploring the emergence of spatio-temporal patterns due to nonlinearities in gene expression is a relatively new development. In this work, we explore the effect of resource constraint on gene regulatory motif from both equilibrium and spatio-temporal standpoint, taking into consideration the degradation class of resource, protease. We have demonstrated that protease-tagged degradation can cause an emergent bistability to form in the system in a steady-state scenario. Instead of a graded linear response in protein synthesis, two Saddle-node bifurcations caused by protease competition provide a switch-like response with hysteresis, where two drastically differing protein concentrations can coexist. We next turn our attention to spatio-temporal analysis: we extend our study for a two-dimensional sheet of cells with diffusible protein molecules and report the stationary patterns.To investigate the reasons behind these non-homogeneous stationary patterns, we investigate the traveling wave solution and observe that a stationary pattern is formed by the traveling wave solution. Considering that proteases play a major role in the regulation and expression of genes in a variety of diseased scenarios, the repercussions of this spatial patterning caused by protease competition can be extensive in gene regulatory systems.

synthetic biology↗

bioRxiv2025

A dominant role of cell death in limiting Chandipura virus propagation at cell-saturating high multiplicity of infection

Viruses transit from a low to high multiplicity of infection (MOI) regime in infected tissues. Type-1 interferons (IFNs) enforce a cellular state refractory to virus multiplication, while the death of infected cells eliminates viral replicative niche. Here, we investigated how these two innate antiviral mechanisms cooperate at various MOIs upon cell infection by Chandipura virus (CHPV), a cytopathic RNA virus implicated in several outbreaks of acute encephalitis in India. We found that as expected, a gradual increase in the input MOI from 0.02 to 2 led to a proportionate surge in the viral yield. Surprisingly, a further rise to MOI 20 caused a reduction in the progeny titer. Our mathematical modeling together with ex vivo infection studies involving mutant cells suggested that cell death - more so than virus-induced type-1 IFNs - restricted CHPV propagation at cell-saturating high MOIs, leading to a net fall in the yield at MOI 20. We argue that the distinct involvement of innate immune pathways at varied MOIs imparts robust cellular defense against cytopathic viruses. Significance sentenceCell death - more so than type-1 interferons - limits Chandipura virus propagation at cell-saturating high multiplicity of infection. Highlights# Type-1 IFNs and cell death cooperate at varied MOI in limiting CHPV multiplication. # At sub-saturating low MOI, type-1 IFNs play a dominant role in controlling CHPV propagation. # At cell-saturating high MOI, cell death determines the progeny yield.

systems biology↗

bioRxiv2025

Breast cancer cell migration is potentiated by associated fibroblasts through a laminin-511-driven cortical localization of Arp2/3

Invading cancer cells are intermingled with fibroblasts that interact with them to regulate their migration, although the precise motility-driving signaling mechanisms initiated upon such interactions remain ill-understood. We constitute time-lapse-tractable 3D pathotypic cultures with breast cancer cell lines with fibroblasts enriched from invasive ductal carcinoma biopsies. Herein, cancer-associated fibroblasts (CAFs) enhanced breast cancer migration relative to non-cancerous fibroblasts (NFs), also observed through greater infiltration of orthotopically injected cancer cells within murine inguinal lymph nodes. The enhancement was also seen in cancer cells exposed to CAF-secreted medium. CAFs phenocopied laminin-rich matrix in compacting cancer cell clusters. A subsequent immunocytochemical screen identified laminins 5, -{beta}1, and -{gamma}1 to be highly expressed in enriched CAFs populations as well as in stromal areas of breast cancer sections. Depleting laminin-5, -{beta}1, and -{gamma}1 in CAFs downregulated 3D cancer cell migration. Cancer cells cultivated on Laminin-511 substrata showed increased adhesion, faster and persistent migration, enhanced shape polarization, and deformability of cancer cells relative to Laminin-211 controls. Observation of higher invadopodial F-actin dynamics on Laminin-511 led us to assay for and demonstrate anisotropically corticalized Arp 2/3 in cancer cells. An integrin antibody screen showed Integrin 6{beta}1 inhibition specifically nullified Laminin-511-driven enhancement of morphomigrational traits of cancer cells, similar to Arp2/3 inhibition. Moreover, cells on Laminin-511 showed enhanced Integrin 6 localization to their invadopodia. We propose that activated fibroblasts use Laminin-511 to localize cognate integrin receptors, and Arp2/3 of cancer cells to their invadopodia, resulting in higher Arp2/3-driven actin remodeling and enhanced cell migration.

cancer biology↗

bioRxiv2025

A PKM2-YAP reciprocal repartitioning modulates invasion of breast cancer cells

Invasive cancer cells exhibit distinct morphomigrational and metabolic traits when confronted with biophysically variant matrix microenvironments enroute metastasis. Whether dynamical shifts in such traits are interlinked through a common molecular program remains ill-understood. Using triple negative breast cancer cell lines on Collagen I substrata coated hydrogels recapitulating stiffness values of non-cancerous breast tissue and the desmoplasia of tumors, we observed greater cell shape polarization and migration in the latter. Associated lower lactate and pyruvate levels in such conditions motivated us to examine their pyruvate kinase M2 expression, which showed nuclear and cytoplasmic localization in softer and stiffer environments respectively. Pharmacologically impairing PKM2 activity in stiffer substrata decreased migration and shape polarization of cancer cells while increasing lactate and pyruvate levels. In contrast, increasing its activity on softer substrata attenuated cancer cell migration and elongation. We assayed for localization of the mechanosensory protein YAP upon PKM2 activity modulation: PKM2 activation increased nuclear YAP localization on soft substrata. Pharmacologically inhibiting YAP on stiff substrata not just decreased migration but also increased nuclear localization of PKM2 and lactate and pyruvate levels. We propose that a reciprocal repartitioning of PKM2-YAP interlinks the cognate metabolic and migrational states of cancer cells; targeting such positive feedback may hold the key to future therapeutic strategies.

cancer biology↗

bioRxiv2025

AGAAT: Automated computational tool integrating different genotyping array and correctional methods for data analysis

Genotyping arrays are widely used in studying the genetics of complex diseases. Arrays with multi-ethnic markers enable population-scale and cost-effective genetic studies in underrepresented populations. But automated pipelines that convert raw data files into association results are lacking for these genotyping arrays. Also, combining variant files from multiple genotyping projects is difficult due to differences arising from multiple versions of standard file formats like Variant Calling Format (VCF). We have developed an automated tool named AGAAT (Automated Genotyping Array Analysis Tool) to overcome these problems. In addition to the automated pipelines for multi-ethnic arrays, we have added additional Python scripts for multiple testing correction using haplotype blocks, candidategene analysis, candidate-gene common-variant analysis and addition of 1000 genome phase-3 genotype counts to the controls, followed by case-control association analysis.

bioinformatics↗

bioRxiv2025

Identifying a logical specification and a program for an LLM-based generator of lead molecules

Our interest is in the generation of "lead" molecules in early-stage drug design. Leads are small molecules (ligands) that can bind to a part of pre-specified target and also satisfy multiple physico-chemical constraints. We propose using techniques developed in Inductive Logic Programming (ILP) to identify a logical specification of feasible molecules; and then using this specification to construct a program that uses a large language model (LLM) to generate new molecules. We ensure the program constructed is correct, in the sense that every molecule generated by the program is feasible according the specification. Our focus is on contributing to on-going drug-discovery research on novel inhibitors for Dopamine {beta}-hydroxylase (DBH), an enzyme that plays a pivotal role in several diseases related to the brain and the heart. We find molecules comparable in affinity to the latest generation drugs currently in clinical trials, and chemical assessment of synthesisablity of the molecules generated. For completeness, we also provide results obtained on the classic benchmark datasets used in recent work reported in [1].

bioinformatics↗

bioRxiv2025

Neur-Ally: A deep learning model for regulatory variant prediction based on genomic and epigenomic features in brain and its validation in certain neurological disorders

Large scale quantitative studies have identified significant genetic associations for various neurological disorders. Expression quantitative trait loci [eQTL] studies have shown the effect of single nucleotide polymorphisms [SNPs] on the differential expression of genes in brain tissues. However, a large majority of the associations are contributed by SNPs in the noncoding regions which can have significant regulatory function but are often ignored. Besides mutations that are in high linkage disequilibrium [LD] with actual regulatory SNPs will also show significant associations. Therefore, it is important to differentiate a regulatory non-coding SNPs with a non-regulatory one. To resolve this, we developed a deep-learning model named Neur-Ally, which was trained on epigenomic datasets from nervous tissue and cell line samples. The model predicts differential occurrence of regulatory features like chromatin accessibility, histone modifications and transcription-factor [TF] binding on genomic regions using DNA sequence as input. The model was used to predict the regulatory effect of neurological condition specific non-coding SNPs using in-silico mutagenesis. The effect of associated SNPs reported in Genome-wide association studies [GWAS] of neurological condition, Brain eQTLs, Autism Spectrum Disorder [ASD] and reported probable regulatory SNPs in neurological conditions were predicted by Neur-Ally.

bioinformatics↗

bioRxiv2024

Nanomaterials trigger functional responses in primary human immune cells

Targeting the immune system with nanoparticles (NPs) to deliver immunomodulatory molecules emerged as a solution to address intra-tumoral immunosuppression and enhance therapeutic response. While the potential of nanoimmunotherapies in reactivating immune cells has been evaluated in several preclinical studies, the impact of drug-free nanomaterials on the immune system remains unknown. Here, we characterize the molecular and functional response of human NK cells and pan T cells to a selection of five NPs that are commonly used in biomedical applications. After a pre-screen to evaluate the toxicity of these nanomaterials on immune cells, we selected ultrasmall silica-based gadolinium (Si-Gd) NPs and poly(lactic-co-glycolic acid) (PLGA) NPs for further investigation. Bulk RNA-sequencing and flow cytometry analysis showcase that PLGA NPs trigger a transcriptional priming towards activation in NK and pan T cells. While PLGA NPs improved NK cells anti-tumoral functions in cytokines-deprived environment, Si-Gd NPs significantly impaired T cells activation as well as functional responses to a polyclonal antigenic stimulation. Altogether, we identified PLGAs NPs as suitable and promising candidates for further targeting approaches aiming to reactivate the immune system of cancer patients.

immunology↗

bioRxiv2024

Molecular Evolution and Functional Divergence of Heterodisulfide Reductase A (HdrA)

Heterodisulfide reductase is a key enzyme in methanogenesis pathway in archaea, which helps to recycle the coenzymes after methane is formed from C1 carbon sources. Homologous enzymes are observed in non-methanogenic archaea and prokaryotes but their functional and evolutionary details are not fully explored. This report aims at understanding the distribution of one such homologous enzyme, heterodisulfide reductase A (HdrA); its domain architecture, overall structural contribution in biological function and evolutionary details in organisms other than methanogen. Exhaustive sequence analysis from both archaea and prokaryotic lineages reveals the presence of highly conserved homologues which probably have an altered oxido-reductase function. Phylogenetic analysis and co-clustering showed the differential diversity of the homologues enzyme in metabolically diverse groups. The distribution of Heterodisulfide homologues in both archaea and prokaryotes shows differential expansion of this protein by multiple horizontal gene transfer events. Conserved domain analysis and structural modelling of different phylogenetic clades shows sequence and structural diversity at the C-terminal domain. Bimolecular network analysis highlights the functional association and interactions of the heterodisulfide homologues with diverse protein partners which participate in different metabolic function. HdrA involved in species specific metabolic function while the functional conservation is evident between close related species. Analysis of structural domain within HdrAs reveals that clade specific sequence which helps to differentiate structural domain arrangement and contributes to functional constrains. The presence of HdrA protein in methanogenic archaea and non-methanogens suggests that the protein function involving redox reaction and electron transfer shared a common history.

bioinformatics↗

bioRxiv2024

Chemical inactivation of two non-enveloped viruses follows distinct molecular pathways

Non-enveloped viruses, which lack a lipid envelope, typically display higher resistance to disinfectants, soaps and sanitizers compared to enveloped viruses. The capsids of these viruses are highly stable and symmetric protein shells that resist inactivation by commonly employed virucidal agents. This group of viruses include highly transmissible human pathogens such as Rotavirus, Poliovirus, Foot and Mouth Disease Virus, Norovirus and Adenovirus; thus, devising appropriate strategies for chemical disinfection is essential. We tested a mild combination of a denaturant, alcohol, and organic acid on two representative non-enveloped viruses - Human Adenovirus 5 (HAdV5) and Feline Calicivirus (FCV)- and evaluated the molecular pathway of capsid neutralization using biophysical methods. The transition temperatures signifying conformational shifts in the capsid were established in the presence and absence of chemical treatment using Differential Scanning Calorimetry (DSC), while the corresponding morphological alterations were visualized and correlated using Transmission Electron Microscopy (TEM). We found that while chemical treatment of purified HAdV5 particles resulted in increased thermal instability, followed by large scale particle aggregation; similar treatment of FCV particles resulted in complete collapse of the capsids. The distinct effects of the chemical treatment on the morphology of HAdV5 and FCV suggests that non-enveloped viruses with icosahedral geometry can follow different molecular pathways to inactivation. Further, while individual components of the chemical formulation caused significant damage to the capsids, a synergistic action of the whole formulation was evident against both non-enveloped viruses tested. Molecular level understanding of inactivation pathways may result in the design and development of effective mass-market formulations for rapid neutralization of non-enveloped viruses. HighlightsO_LIformulation consisting of 3.2% citric acid, 1% urea in 70% ethanol, pH4 effectively inactivates HAdV5 and FCV. C_LIO_LIinactivation pathways with complete formulation, are different for the two viruses. C_LIO_LIeffect of whole formulation is more effective compared to individual components. C_LI

microbiology↗

bioRxiv2024

Unfolded Von Willebrand Factor Binds Protein S and Reduces Anticoagulant Activity

Protein S (PS), the critical plasma cofactor for the anticoagulants tissue factor (TF) pathway inhibitor (TFPI) and activated protein C (APC), circulates in two functionally distinct pools: free (anticoagulant) or bound to complement component 4b-binding protein (C4BP) (anti-inflammatory). Acquired free PS deficiency is detected in several viral infections, but its cause is unclear. Here, we identified a shear-dependent interaction between PS and von Willebrand Factor (VWF) by mass spectrometry. Consistently, plasma PS and VWF comigrated in both native and agarose gel electrophoresis. The PS/VWF interaction was blocked by TFPI but not APC, suggesting an interaction with the C-terminal sex hormone binding globulin (SHBG) region of PS. Microfluidic systems, mimicking arterial laminar flow or disrupted turbulent flow, demonstrated that PS stably binds VWF as VWF unfolds under turbulent flow. PS/VWF complexes also localized to platelet thrombi under laminar arterial flow. In thrombin generation-based assays, shearing plasma decreased PS activity, an effect not seen in the absence of VWF. Finally, free PS deficiency in COVID-19 patients, measured using an antibody that binds near the C4BP binding site in SHBG, correlated with changes in VWF, but not C4BP, and with thrombin generation. Our data suggest that PS binds to a shear-exposed site on VWF, thus sequestering free PS and decreasing its anticoagulant activity, which would account for the increased thrombin generation potential. As many viral infections present with free PS deficiency, elevated circulating VWF, and increased vascular shear, we propose that the PS/VWF interaction reported here is a likely contributor to virus-associated thrombotic risk. Key PointsO_LIVon Willebrand Factor (VWF) binds Protein S (PS) in a shear-dependent manner, reducing the free PS pool and its anticoagulant activity. C_LIO_LIThe PS/VWF complex forms under turbulent flow conditions, is stable in whole blood, and localizes to growing platelet thrombi. C_LI

biochemistry↗

bioRxiv2023

Combinatorial cooperativity can facilitate epithelial-mesenchymal transition in a miR200-Zeb feedback network

Carcinoma cells often utilize epithelial-mesenchymal transition (EMT) programs for cancer progression and metastasis. Numerous studies point to the SNAIL-induced miR200/Zeb feedback circuit as crucial in regulating EMT by shifting cancer cells to at least three (epithelial (E), hybrid (h E/M), mesenchymal (M)) phenotypic states arrayed along the epithelial-mesenchymal phenotypic spectrum. However, a coherent molecular-level understanding of how such a tiny circuit controls carcinoma cell entrance into and residence in various states is lacking. Here, we use molecular binding data and mathematical modeling to report that miR200/Zeb circuit can essentially utilize combinatorial cooperativity to control E-M phenotypic plasticity. We identify minimal combinatorial cooperativities that give rise to E, hybrid-E/M, and M phenotypes. We show that disrupting a specific number of miR200 binding sites on Zeb as well as Zeb binding sites on miR200 can have phenotypic consequences - the circuit can dynamically switch between two (E, M) and three (E, hybrid-E/M, M) phenotypes. Further, we report that in both SNAIL-induced and SNAIL knock-out miR200/Zeb circuits, cooperative transcriptional feedback on Zeb as well as Zeb translational inhibition due to miR200 are essential for the occurrence of intermediate hybrid-E/M phenotype. Finally, we demonstrate that SNAIL can be dispensable for EMT, and in the absence of SNAIL, the transcriptional feedback can control cell state transition from E to hybrid-E/M, to M state. Our results thus highlight molecular-level regulation of EMT in miR200/Zeb circuit and we expect these findings to be crucial to future efforts aiming to prevent EMT-facilitated dissemination of carcinomas.

cancer biology↗

bioRxiv2023

Downregulation of a cell polarity protein potentiates Chikungunya Virus infection in host cells

During cellular infections, alphaviruses produce a 6 kDa membrane protein (6K) and a transframe variant (TF) of 6K through ribosomal frameshifting. The role of these proteins in alphavirus biology is largely unknown. Here, we show that TF of Chikungunya virus plays a unique and critical role in promoting virus propagation by manipulating host cell boundaries. TF achieves this by targeting and downregulating human Scribble, a component of the polarity complex that controls cellular morphology and apoptosis, leading to its punctate localization, ubiquitination, and subsequent degradation via the proteasomal pathway. The TF-Scribble interaction is mediated by a newly discovered PDZ-domain binding motif (PBM) in TF, with the PDZ domains of Scribble, as demonstrated by co-localization during viral infection and further by co-immunoprecipitation and proteomics analysis. This PBM is unique to TF and is absent in 6K; thus, 6K cannot modulate Scribble localization in infected cells. shRNA-mediated knockdown of Scribble potentiates CHIKV propagation highlighting the requirement of TF for the downregulation of Scribble. While wildtype CHIKV drastically alters cell-cell boundaries, a mutated version of CHIKV generated through reverse genetics ({Delta}TF CHIKV), which produces 6K but not TF, is unable to trigger similar morphological alterations due to its inability to engage Scribble, ultimately resulting in suboptimal virus propagation. A cryoEM reconstruction of {Delta}TF CHIKV at a global resolution of 3.6 [A], one of the highest reported among all alphavirus structures, indicates that the assembly of glycoprotein spikes and nucleocapsid is unaffected. Thus, the loss of TF affects the ultimate stage of cellular egress in the virus life cycle, and not earlier stages such as entry, replication or assembly. Our work thus establishes a novel function for the TF component of alphaviruses in modulating host morphology, potentiating virus transmission, and also distinguishes the functionality of TF from that of 6K in alphavirus biology. TeaserA novel functionality of Chikungunya Virus in modulating cell boundaries to allow efficient virus propagation

cell biology↗

bioRxiv2023

Chimeric chikungunya virus-like particles with surface exposed SARS-CoV-2 RBD elicits potent immunogenic responses in mice.

The SARS-CoV-2 pandemic has reinforced efforts for developing effective vaccination strategy for existing and emerging viruses. Currently there are various vaccine technology available for treating viral diseases, however it is imperative to develop and investigate second-generation vaccines such as chimeric virus-like particles (chi-VLPs) vaccine for increased immunogenicity, ease of production and scalability to supplement the worldwide vaccine supply. Intriguingly, chi-VLPs expresses more than one antigenic epitope on its surface, hence it is expected to be a more effective vaccine candidate. Hereby, this study reports, a novel bivalent vaccine design of chimeric alphavirus coronavirus virus-like particles (ChAC-VLPs), displaying fusion glycoproteins of CHIKV and receptor binding domain (RBD) of SARS-CoV-2 on its surface. Uniqueness and versatility of ChAC-VLPs has been demonstrated via a various techniques including Western blot, Immunofluorescence, cryoEM, and dynamic light scattering (DLS). The multimeric epitope display of immunogenic antigens, i.e CHIKV envelop glycoprotein and SARS-CoV-2 RBD was validated by cell-based assays. ChAC-VLP immunized mice has shown substantial neutralization titres for CHIKV (PRNT50 of 1:25) from the serum collected after 2nd booster doses. Similarly, serum antibodies were detected for SARS-CoV2 RBD as observed by antigen specific ELISA and validated using surface plasmon resonance (SPR). SPR binding response was detected to be >200 RU for anti-RBD antibody in post-immunized mice sera. In conclusion, present study proposes ChAC-VLPs as a potential hybrid vaccine candidate for CHIKV and SARS-CoV-2 infection and contributes valuable insights in chi-VLPs domain.

molecular biology↗

bioRxiv2022

Genetic affinities and adaptation of the South West coast populations of India

Evolutionary event has not only transformed the genetic structure of human populations but also associated with social and cultural transformation. South Asian populations were formed as a result of such evolutionary events of migration and admixture of genetically and culturally distinct groups. Most of the genetic studies pointed to large-scale admixture event between Ancestral North Indian (ANI) and Ancestral South Indian (ASI) groups, also additional layers of recent admixture. In the present study we have analyzed 213 individuals inhabited in South West coast India with traditional warriors and feudal lord status and historically associated with recent migrations events and possible admixture with Indo-Scythians, Saka, Huns and Kushans, whose genetic links are still missing. Analysis of autosomal SNP markers suggests that these groups possibly derived their ancestry from some groups of North West India having additional Middle Eastern genetic component and also their separation history suggests very early separation from North West Indian and Gangetic plain Indo-Europeans during late bronze or Iron age, most probably following central India and Godavari basin to South West coast. Higher distribution of west Eurasian mitochondrial haplogroups also points to admixture through maternal lineage. Selection screen using genome wide genealogy approach revealed genetic signatures related to their long-term coastal food habits. Thus, our study suggests that the South West coastal groups with traditional warriors and feudal lords status are of a distinct lineage compared to Dravidian and Gangetic plain Indo-Europeans and are remnants of very early migrations from North West India following Godavari basin to Karnataka and Kerala.

genetics↗

bioRxiv2021

Galectin-9 signaling drives breast cancer invasion through matrix

Aberration in expression and function of glycans and their binding proteins (lectins) in transformed cells constitutes one of the earliest discovered hallmarks of cancer. Galectins are a conserved family of lectins that can bind to {beta}-galactosides. Among them, the role of Galectin-9, a galectin with two carbohydrate binding domains in immune-tumor cell interactions has been well-established, although its effect on cancer cell behavior remains as yet unclear. In this study, we used a spectrum of cell lines from homeostatic breast cells to transformed non-invasive and invasive cell lines cultured in microenvironment-diverse conditions to show that Galectin-9 expression shows an elevation in association with invasiveness of breast cancer epithelia. Our observations were supported by immunohistochemical studies of breast tumors and adjacent normal-tissues from patients. Genetic perturbation of Galectin-9 as well as the pharmacological inhibition of activity using cognate inhibitors confirmed a positive correlation between Galectin-9 levels and the adhesion of the aggressive triple negative breast cancer cells MDA-MB-231 to- and their invasion through-extracellular matrices (ECM). Within a constituted organomimetic multiECM microenvironment, Galectin-9 enhanced both the solitary and the collective invasion of cancer cells. Quantitative proteomics led us to uncover the inductive role of Galectin-9 in the expression of the proinvasive protein S100A4. In addition, Galectin-9 expression correlated with FAK signaling, the inhibition of which decreased S100A4 mRNA levels. Our results provide crucial signaling insights into how the elevation in Galectin-9 expression in breast cancer cells potentiates their invasiveness through ECM during early steps of metastasis.

cancer biology↗