Cancer metastasis is a complex mechanism involving multiple processes. In an earlier study, we reported that the levels of serine/threonine phosphatase POPX2were 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 on public databases shows that low POPX2 expression is linked to poor survival rate and patients with distant metastasis.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. Secretomeanalysis of POPX2-knockdown MDA-MB-231 cells using LC-MS/MS based SILAC quantitative proteomics and cytokine arrayshow that silencing of POPX2 leads to increased secretion of exosomes, which may in turn induce multiple pro-angiogenic cytokines.This study, combined with our earlier findings,suggeststhat a single ubiquitously expressed phosphatase POPX2 influences cancer metastasisvia modulating multiple biological processes including MAPK signaling and exosome-cytokine secretion.
[dataset license: CC0 1.0 Universal (CC0 1.0)]
Keywords: Tumor angiogenesis ; secretome ; exosome ; cytokine ; POPX2 phosphatase ; SILAC mass spectrometry
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Principal Investigators: (in alphabetical order) |
Cheng Gee Koh, Nanyang Technological University School of Biological Science, N/A |
| Submitting User: | ccms |
Zhang S, Weng T, Cheruba E, Guo T, Chan H, Sze SK, Koh CG.
Phosphatase POPX2 Exhibits Dual Regulatory Functions in Cancer Metastasis.
J. Proteome Res. 2017 Feb 3;16(2):698-711. Epub 2016 Dec 28.
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