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Sakamoto, M.

Publications and source records attributed to Sakamoto, M..

28 records · Page 2Linked to original sources

Targeting c-Jun is a potential therapy of luminal breast cancer bone metastasis

Luminal breast cancer has the highest bone metastasis frequency among all breast cancer subtypes, but its metastatic mechanism has not been elucidated because of the lack of appropriate metastatic cell lines. The study aim was to characterize high-osteolytic bone metastatic MCF7-BM cell lines and extract c-Jun, a novel bone metastasis marker. We found that c-Jun was upregulated in MCF7-BM cells, and its deficiency was associated with suppression of the cell migration, transformation, and stemness of BM cells. In vivo, c-Jun-deficient MCF7-TAM67 cells exhibited weaker bone metastatic ability. Additionally, c-Jun overexpression in MCF7-BM cells led to a tumor-migration promotion cycle in the bone microenvironment possibly by enhancing calcium-induced migration and releasing the osteoclast activator BMP5. Inhibition of c-Jun by JNK-IN-8, a JNK inhibitor, effectively reduced tumorigenesis activities and bone metastatic tumors. Our results indicate the potential benefits of a therapy that targets c-Jun to prevent or minimize luminal breast cancer bone metastasis.

cancer biology↗

Fucosyltransferase 8 (FUT8) and core fucose expression in oxidative stress response

GlycoMaple is a new tool to predict glycan structures based on the expression levels of 950 genes encoding glycan biosynthesis-related enzymes and proteins using RNA-seq data. The antioxidant response, protecting cells from oxidative stress, has been focused on because its activation may relieve pathological conditions, such as neurodegenerative diseases. Genes involved in the antioxidant response are defined within the GO:0006979 category, including 441 human genes. Fifteen genes overlap between the glycan biosynthesis-related genes defined by GlycoMaple and the antioxidative response genes defined by GO:0006979, one of which is FUT8. 5-Hydroxy-4-phenyl-butenolide (5H4PB) extracted from Chinese aromatic vinegar induces the expression of a series of antioxidant response genes that protect cells from oxidative stress via activation of the nuclear factor erythroid 2-related factor 2-antioxidative response element pathway. Here, we show that FUT8 is upregulated in both our RNA-seq data set of 5H4PB-treated cells and publicly available RNA-seq data set of cells treated with another antioxidant, sulforaphane. Applying our RNA-seq data set to GlycoMaple led to a prediction of an increase in the core fucose of N-glycan that was confirmed by flow cytometry using a fucose-binding lectin. These results suggest that FUT8 and core fucose expression may increase upon the antioxidant response.

pharmacology and toxicology↗

MarpolBase Expression: A Web-based, Comprehensive Platform for Visualization and Analysis of Transcriptomes in the Liverwort Marchantia polymorpha

The liverwort Marchantia polymorpha is equipped with a wide range of molecular and genetic tools and resources that have led to its wide use to explore the evo-devo aspects of land plants. Although its diverse transcriptome data are rapidly accumulating, there is no extensive yet user-friendly tool to exploit such a compilation of data and to summarize results with the latest annotations. Here, we have developed a web-based suite of tools, MarpolBase Expression (MBEX, https://marchantia.info/mbex/), where users can visualize gene expression profiles, identify differentially expressed genes, perform co-expression and functional enrichment analyses, and summarize their comprehensive output in various portable formats. Using oil body biogenesis as an example, we demonstrated that the results generated by MBEX were consistent with the published experimental evidence and also revealed a novel transcriptional network in this process. MBEX should facilitate the exploration and discovery of the genetic and functional networks behind various biological processes in M. polymorpha, and promote our understanding of the evolution of land plants.

plant biology↗

HOXB7 induces oncogenic transformation in NMuMG cells via JAK2-STAT3 signaling

The homeobox family genes are often dysregulated in a various cancer type. Particularly HOXB7 amplification and overexpression correlate with poor prognosis in various cancer such as gastric, pancreatic, and lung cancers. Moreover, HOXB7 is known to contribute to cancer progression by promoting epithelial to mesenchymal transition, anti-cancer drug resistance, and angiogenesis. In this study, we show that HOXB7 is coamplified with ERBB2 in a subset of breast cancer patients and HOXB7 expression correlates with poor prognosis in HER2-positive breast cancer patients. This clinical observation is supported by the following results: HOXB7 overexpression in an immortalized murine mammary gland epithelial cell line NMuMG induces cellular transformation in vitro, tumorigenesis and lung metastasis through the activation of JAK-STAT signaling.

cancer biology↗

Genome evolution of a non-parasitic secondary heterotroph, the diatom Nitzschia putrida

Secondary loss of photosynthesis is observed across almost all plastid-bearing branches of the eukaryotic tree of life. However, genome-based insights into the transition from a phototroph into a secondary heterotroph have so far only been revealed for parasitic species. Free-living organisms can yield unique insights into the evolutionary consequence of the loss of photosynthesis, as the parasitic lifestyle requires specific adaptations to host environments. Here we report on the diploid genome of the free-living diatom Nitzschia putrida (35 Mbp), a non-photosynthetic osmotroph whose photosynthetic relatives contribute ca. 40% of net oceanic primary production. Comparative analyses with photosynthetic diatoms revealed that a combination of genes loss, the horizontal acquisition of genes involved in organic carbon degradation, a unique secretome and the rapid divergence of conserved gene families involved in cell wall and extracellular metabolism appear to have facilitated the lifestyle of a non-parasitic, free-living secondary heterotroph.

genomics↗

Assessing bite force estimates in extinct mammals and archosaurs using phylogenetic predictions

Bite force is an ecologically important biomechanical performance measure is informative in inferring the ecology of extinct taxa. However, biomechanical modelling to estimate bite force is associated with some level of uncertainty. Here, I assess the accuracy of bite force estimates in extinct taxa using a Bayesian phylogenetic prediction model. I first fitted a phylogenetic regression model on a training set comprising extant data. The model predicts bite force from body mass and skull width while accounting for differences owning to biting position. The posterior predictive model has a 93% prediction accuracy as evaluated through leave-one-out cross-validation. I then predicted bite force in 37 species of extinct mammals and archosaurs from the posterior distribution of predictive models. Biomechanically estimated bite forces fall within the posterior predictive distributions for all except four species of extinct taxa, and are thus as accurate as that predicted from body size and skull width, given the variation inherent in extant taxa and the amount of time available for variance to accrue. Biomechanical modelling remains a valuable means to estimate bite force in extinct taxa and should be reliably informative of functional performances and serve to provide insights into past ecologies.

evolutionary biology↗

Collection of 2429 constrained headshots of 277 volunteers for deep learning

Deep learning has rapidly been filtrating many aspects of human lives. In particular, image recognition by convolutional neural networks has inspired numerous studies in this area. Hardware and software technologies as well as large quantities of data have contributed to the drastic development of the field. However, the application of deep learning is often hindered by the need for big data and the laborious manual annotation thereof. To experience deep learning using the data compiled by us, we collected 2429 constrained headshot images of 277 volunteers. The collection of face photographs is challenging in terms of protecting personal information; we established an online procedure in which both the informed consent and image data could be obtained. We did not collect personal information, but issued agreement numbers to deal with withdrawal requests. Gender and smile labels were manually and subjectively annotated only from the appearances, and final labels were determined by majority among our team members. Rotated, trimmed, resolution-reduced, decolorized, and matrix-formed data were allowed to be publicly released. Moreover, simplified feature vectors for data sciences were released. We performed gender recognition by building convolutional neural networks based on the Inception V3 model with pre-trained ImageNet data to demonstrate the usefulness of our dataset.

animal behavior and cognition↗

AnAms1.0: A high-quality chromosome-scale assembly of a domestic cat Felis catus of American Shorthair breed

The domestic cat (Felis catus) is one of the most popular companion animals in the world. Comprehensive genomic resources will aid the development and application of veterinary medicine including to improve feline health, in particular, to enable precision medicine which is promising in human application. However, currently available cat genome assemblies were mostly built based on the Abyssinian cat breed which is highly inbred and has limited power in representing the vast diversity of the cat population. Moreover, the current reference assembly remains fragmented with sequences contained in thousands of scaffolds. We constructed a reference-grade chromosome-scale genome assembly of a domestic cat, Felis catus genome of American Shorthair breed, Anicom American shorthair 1.0 (AnAms1.0) with high contiguity (scaffold N50 > 120 Mb), by combining multiple advanced genomic technologies, including PacBio long-read sequencing as well as sequence scaffolding by long-range genomic information obtained from Hi-C and optical mapping data. Homology-based and ab initio gene annotation was performed with the Iso-Seq data. Analyzed data is be publicly accessible on Cats genome informatics (Cats-I, https://cat.annotation.jp/), a cat genome database established as a platform to facilitate the accumulation and sharing of genomic resources to improve veterinary care.

genomics↗

MGSE regulates crosstalk from the mucin pathway to the TFE3 pathway of the Golgi stress response

The Golgi apparatus is an organelle where membrane or secretory proteins receive post-translational modifications such as glycosylation and sulfation, after which the proteins are selectively transported to their final destinations through vesicular transport. When the synthesis of secretory or membrane proteins is increased and overwhelms the capacity of the Golgi (Golgi stress), eukaryotic cells activate a homeostatic mechanism called the Golgi stress response to augment the capacity of the Golgi. Four response pathways of the Golgi stress response have been identified, namely the TFE3, CREB3, HSP47, and proteoglycan pathways, which regulate the general function of the Golgi, apoptosis, cell survival, and proteoglycan glycosylation, respectively. Here, we identified a novel response pathway that augments the expression of glycosylation enzymes for mucins in response to insufficiency in mucin-type glycosylation in the Golgi (mucin-type Golgi stress), and we found that expression of glycosylation enzymes for mucins such as GALNT5, GALNT8, and GALNT18 was increased upon mucin-type-Golgi stress. We named this pathway the mucin pathway. Unexpectedly, mucin-type Golgi stress induced the expression and activation of TFE3, a key transcription factor regulating the TFE3 pathway, suggesting that the activated mucin pathway sends a crosstalk signal to the TFE3 pathway. We identified an enhancer element regulating transcriptional induction of TFE3 upon mucin-type Golgi stress, and named it the mucin-type Golgi stress response element, of which consensus was ACTTCC(N9)TCCCCA. These results suggested that crosstalk from the mucin pathway to the TFE3 pathway has an important role in the regulation of the mammalian Golgi stress response.

cell biology↗

Extreme and rapid bursts of functional adaptations shape bite force in amniotes

Adaptation is the fundamental driver of functional and biomechanical evolution and can be linked to rates of phenotypic trait evolution. Significant shifts in evolutionary rates are seen as instances of exceptional adaptation. However, whether or not signatures of exceptional adaptations (elevated rates) can be distinguished from general adaptations (background rate) in biomechanical traits remains to be tested in a robust statistical framework. Here, we apply a recently developed phylogenetic statistical approach for detecting exceptional adaptations in bite force, in a large group of terrestrial vertebrates, the amniotes. Our results show that bite force in amniotes evolved through multiple bursts of exceptional changes, whereby whole groups - including Darwin';s finches, maniraptoran dinosaurs (group of non-avian dinosaurs including birds), anthropoids and hominins (the group of species including modern humans) - experienced significant rate increases compared to the background rate. However, in most parts of the amniote tree of life we find no exceptional rate increases, indicating that coevolution with body size was primarily responsible for the patterns observed in bite force. Our approach represents a template for future studies in functional morphology and biomechanics, where exceptional functional adaptations can be quantified and potentially linked to specific ecological factors underpinning major evolutionary radiations.

evolutionary biology↗