Biology subjects

Tripathy, D.

Publications and source records attributed to Tripathy, D..

4 recordsLinked to original sources

bioRxiv2021

Lipocalin 2 promotes inflammatory breast cancer tumorigenesis and skin invasion

Inflammatory breast cancer (IBC) is an aggressive form of primary breast cancer characterized by rapid onset and high risk of metastasis and poor clinical outcomes. The biological basis for the aggressiveness of IBC is still not well understood and no IBC-specific targeted therapies exist. In this study we report that lipocalin 2 (LCN2), a small secreted glycoprotein belonging to the lipocalin superfamily, is expressed at significantly higher levels in IBC versus non-IBC tumors, independently of molecular subtype. LCN2 levels were also significantly higher in IBC cell lines and in their culture media than in non-IBC cell lines. High expression was associated with poor-prognosis features and shorter overall survival in IBC patients. Depletion of LCN2 in IBC cell lines reduced proliferation, colony formation, migration, and cancer stem cell populations in vitro, and inhibited tumor growth, skin invasion, and brain metastasis in mouse models of IBC. Analysis of our proteomics data showed reduced expression of proteins involved in cell cycle and DNA repair in LCN2-silenced IBC cells. Our findings support that LCN2 promotes IBC tumor aggressiveness and offer a new potential therapeutic target for IBC.

cancer biology↗

bioRxiv2020

Deciphering colchicine like actions of clerodin in terms of microtubule destabilization based mitotic abnormalities, G2/M-phase arrest, and plant polyploidy

Clerodin (C24H34O7), a clerodane diterpenoid, is a bitter principle of Clerodendrum viscosum. The present study aimed to decipher colchicine-like actions of clerodin in terms of microtubule destabilization based mitotic abnormalities, G2-M arrest, and plant polyploidy. Purified clerodin showed increased metaphase frequency in Human Peripheral Blood Lymphocytes (HPBLs), Human Embryonic Kidney cells (HEK-293), and Allium cepa root apical meristem cells. Both squashed slide of the onion root tip and flow cytometric analysis of radish protoplast revealed a significantly increased frequency of polyploid cells. Flow cytometric analysis showed an increase in frequencies of G2-M in MCF-7 cells from 6.10 to 16.25% after clerodin (200g/mL) treatment for 24 h. Confocal microscopy imaging of tubulin in clerodin-treated MCF-7 cells revealed microtubule destabilization. Molecular docking and LIGPLOT analysis indicate that clerodin interact in the colchicine binding site, including, single hydrogen bond with Asn 101 of -tubulin. In summary, our experimental data revealed that clerodin has metaphase arresting, microtubule destabilization, and polyploidy inducing ability similar to colchicine. Molecular docking analysis revealed for the first time that clerodin and colchicine interact at the common site of tubulin residue indicating a common mechanism of action. The results also indicate similar cytotoxic potentialities of both clerodin and colchicine even though they belong to different chemical groups. Thus, clerodin may be used in place of colchicine as a plant polyploidy inducing agent in plant breeding programs in Agriculture.

cell biology↗

bioRxiv2020

NDRG1 expression is an independent prognostic factor in inflammatory breast cancer

NDRG1 is widely described as a metastasis suppressor in breast cancer. However, we found that NDRG1 is critical in promoting tumorigenesis and brain metastasis in mouse models of inflammatory breast cancer (IBC), a rare but highly aggressive form of breast cancer. We hypothesized that NDRG1 is a prognostic marker associated with poor outcome in patients with IBC. Microarray gene expression data from the IBC Consortium dataset were analyzed to compare NDRG1 expression between IBC and non-IBC tumors and among breast cancer subtypes. NDRG1 levels in tissue microarrays from 64 IBC patients were evaluated by immunohistochemical staining with anti-NDRG1 primary antibody (32 NDRG1-low [[≤] median], 32 NDRG1-high [>median]). Overall and disease-free survival (OS and DSS) were analyzed with Kaplan-Meier curves and log-rank test. NDRG1 mRNA expression was higher in IBC than in non-IBC tumors (p=0.007), and in more aggressive HER2+ and basal-like vs luminal IBC subtypes (p<0.0001). Univariate analysis showed NDRG1 expression, tumor grade, disease stage, estrogen receptor (ER) status, and receipt of adjuvant radiation to be associated with OS and DSS. NDRG1-high patients had poorer 10-year OS and DSS than NDRG1-low patients (OS, 19% vs 45%, p=0.0278; DSS, 22% vs 52%, p=0.0139). On multivariable analysis, NDRG1 independently predicted OS (hazard ratio [HR]=2.034, p=0.0274) and DSS (HR=2.287, p=0.0174). NDRG1-high ER-negative tumors had worse outcomes OS, p=0.0003; DSS, p=0.0003; and NDRG1-high tumors that received adjuvant radiation treatment had poor outcomes (OS, p=0.0088; DSS, p=0.0093). NDRG1 correlated positively with aggressive tumor characteristics in IBC and was a significant independent prognostic factor for DSS and OSS in IBC patients. Targeting NDRG1 may represent a novel strategy for improving clinical outcomes for patients with IBC.

cancer biology↗

bioRxiv2020

Decorin, a novel negative modulator of E-cadherin in inflammatory breast cancer

ABSTRACTInflammatory breast cancer (IBC) is a clinically distinct and highly aggressive form of breast cancer with rapid onset and a strong propensity to metastasize. The molecular mechanisms underlying the aggressiveness and metastatic propensity of IBC are largely unknown. Herein, we report that decorin (DCN), a small leucine-rich extracellular matrix proteoglycan, is downregulated in tumors from patients with IBC. Overexpression of DCN in IBC cells markedly decreased migration, invasion, and cancer stem cells in vitro and inhibited IBC tumor growth and metastasis in vivo. Mechanistically, DCN functioned as a suppressor of invasion and tumor growth in IBC by destabilizing E-cadherin and inhibiting EGFR/ERK signaling. DCN physically binds E-cadherin in IBC cells and accelerates its degradation through an autophagy-linked lysosomal pathway. We established that DCN inhibits tumorigenesis and metastasis in IBC cells by negatively regulating the E-cadherin/EGFR/ERK axis. Our findings offer a potential therapeutic strategy for IBC, and provide a novel mechanism for IBC pathobiology.Competing Interest StatementThe authors have declared no competing interest.View Full Text

cancer biology↗