Biology subjects

Shivashankar, G. V.

Publications and source records attributed to Shivashankar, G. V..

3 recordsLinked to original sources

bioRxiv2023

Adhesome Receptor Clustering is Accompanied by the Colocalization of the Associated Genes in the Cell Nucleus

Proteins on the cell membrane cluster to respond to extracellular signals; for example, adhesion proteins cluster to enhance extracellular matrix sensing; or T-cell receptors cluster to enhance antigen sensing. Importantly, the maturation of such receptor clusters requires transcriptional control to adapt and reinforce the extracellular signal sensing. However, it has been unclear how such efficient clustering mechanisms are encoded at the level of the genes that code for these receptor proteins. Using the adhesome as an example, we show that genes that code for adhesome receptor proteins are spatially co-localized and co-regulated within the cell nucleus. Towards this, we use Hi-C maps combined with RNA-seq data of adherent cells to map the correspondence between adhesome receptor proteins and their associated genes. Interestingly, we find that the transcription factors that regulate these genes are also co-localized with the adhesome gene loci, thereby potentially facilitating a transcriptional reinforcement of the extracellular matrix sensing machinery. Collectively, our results highlight an important layer of transcriptional control of cellular signal sensing.

cell biology↗

bioRxiv2022

Deleterious Mechanical Deformation Selects Mechanoresilient Cancer Cells with Enhanced Proliferation and Chemoresistance

Cancer cells derived from secondary tumors can form new distant metastases more efficiently as compared to their primary tumor counterparts. This is partially due to the unfavorable microenvironments encountered by metastasizing cancer cells that result in the survival of a more metastatic phenotype from the original population. However, it is unclear how cancer cells may acquire such metastatic competency after overcoming deleterious mechanical stresses. Here, by forcing cancer cells to flow through small capillary-sized constrictions, we demonstrate that mechanical deformation can select a tumor cell subpopulation that exhibits resilience to mechanical squeezing-induced cell death. Transcriptomic profiling reveals up-regulated proliferation and DNA damage response pathways in this subpopulation, which are further translated into a more proliferative and chemotherapy-resistant phenotype. Our results highlight a potential link between the microenvironmental physical barriers and the enhanced malignancy of metastasizing cancer cells which may potentially be utilized for novel therapeutic strategies in preventing the metastatic spread of cancer cells.

cancer biology↗

bioRxiv2022

Guiding Irregular Nuclear Morphology on Nanopillar Array for Malignancy Differentiation in Tumor cells

For more than a century, abnormal nuclei in tumor cells, presenting subnuclear invaginations and folds on the nuclear envelope, have been known to be associated with high malignancy and poor prognosis. However, current nuclear morphology analysis focuses on the features of the entire nucleus, overlooking the malignancy-related subnuclear features in nanometer scale. The main technical challenge is to probe such tiny and randomly distributed features inside cells. We here employ nanopillar arrays to guide subnuclear features into ordered patterns enabling their quantification as a strong indicator of cell malignancy. Both breast and liver cancer cells were validated, as well as the quantification of nuclear abnormality heterogeneity. The alterations of subnuclear patterns were also explored as effective readouts for drug treatment. We envision this nanopillar-enabled quantification of subnuclear abnormal features in tumor cells opens a new angle in characterizing malignant cells and studying the unique nuclear biology in cancer. TeaserA nanopillar-based assay quantifying the abnormal nuclear morphology in tumor cells at single-cell level.

bioengineering↗