5 research outputs found
DEVELOPMENT OF A NOVEL NON-INVASIVE CANCER DETECTION METHOD THROUGH ENRICHMENT OF CPG-RICH REGIONS IN CELL-FREE DNA
Ph.DDOCTOR OF PHILOSOPHY (FOE
Phosphatase POPX2 Exhibits Dual Regulatory Functions in Cancer Metastasis
Cancer metastasis is a complex mechanism
involving multiple processes.
Previously, our integrative proteome, transcriptome, and phosphoproteome
study reported that the levels of serine/threonine phosphatase POPX2
were positively correlated with cancer cell motility through modulating
MAPK signaling. Surprisingly, here we found that POPX2 knockdown cells
induced more numerous and larger tumor nodules in lungs in longer
term animal studies. Interestingly, our analysis of DNA microarray
data from cancer patient samples that are available in public databases
shows that low POPX2 expression is linked to distant metastasis and
poor survival rate. These observations suggest that lower levels of
POPX2 may favor tumor progression in later stages of metastasis. We
hypothesize that POPX2 may do so by modulation of angiogenesis. Secretome
analysis of POPX2-knockdown MDA-MB-231 cells using LC–MS/MS-based
SILAC quantitative proteomics and cytokine array show that silencing
of POPX2 leads to increased secretion of exosomes, which may, in turn,
induce multiple pro-angiogenic cytokines. This study, combined with
our previous findings, suggests that a single ubiquitously expressed
phosphatase POPX2 influences cancer metastasis via modulating multiple
biological processes including MAPK signaling and exosome cytokine
secretion
Zyxin regulates embryonic stem cell fate by modulating mechanical and biochemical signaling interface
Zyxin regulates mouse embryonic stem cell differentiation by integrating mechanical cues through actin stress fibres and focal adhesions and biochemical cues through YAP signalling
Zyxin Is involved in fibroblast rigidity sensing and durotaxis
Focal adhesions (FAs) are specialized structures that enable cells to sense their extracellular matrix rigidity and transmit these signals to the interior of the cells, bringing about actin cytoskeleton reorganization, FA maturation, and cell migration. It is known that cells migrate towards regions of higher substrate rigidity, a phenomenon known as durotaxis. However, the underlying molecular mechanism of durotaxis and how different proteins in the FA are involved remain unclear. Zyxin is a component of the FA that has been implicated in connecting the actin cytoskeleton to the FA. We have found that knocking down zyxin impaired NIH3T3 fibroblast’s ability to sense and respond to changes in extracellular matrix in terms of their FA sizes, cell traction stress magnitudes and F-actin organization. Cell migration speed of zyxin knockdown fibroblasts was also independent of the underlying substrate rigidity, unlike wild type fibroblasts which migrated fastest at an intermediate substrate rigidity of 14 kPa. Wild type fibroblasts exhibited durotaxis by migrating toward regions of increasing substrate rigidity on polyacrylamide gels with substrate rigidity gradient, while zyxin knockdown fibroblasts did not exhibit durotaxis. Therefore, we propose zyxin as an essential protein that is required for rigidity sensing and durotaxis through modulating FA sizes, cell traction stress and F-actin organization