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....

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Main Authors: Zhang, Songjing, Weng, Ting, Cheruba, Elsie, Guo, Tiannan, Chan, Hei, Sze, Siu Kwan, Koh, Cheng-Gee
Other Authors: School of Biological Sciences
Format: Article
Language:English
Published: 2017
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Online Access:https://hdl.handle.net/10356/82297
http://hdl.handle.net/10220/43514
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Institution: Nanyang Technological University
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spelling sg-ntu-dr.10356-822972023-02-28T17:03:02Z Phosphatase POPX2 Exhibits Dual Regulatory Functions in Cancer Metastasis Zhang, Songjing Weng, Ting Cheruba, Elsie Guo, Tiannan Chan, Hei Sze, Siu Kwan Koh, Cheng-Gee School of Biological Sciences SILAC mass spectrometry Secretome 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. MOE (Min. of Education, S’pore) Accepted version 2017-08-01T09:27:34Z 2019-12-06T14:52:46Z 2017-08-01T09:27:34Z 2019-12-06T14:52:46Z 2016 Journal Article Zhang, S., Weng, T., Cheruba, E., Guo, T., Chan, H., Sze, S. K., et al. (2017). Phosphatase POPX2 Exhibits Dual Regulatory Functions in Cancer Metastasis. Journal of Proteome Research, 16(2), 698-711. 1535-3893 https://hdl.handle.net/10356/82297 http://hdl.handle.net/10220/43514 10.1021/acs.jproteome.6b00748 en Journal of Proteome Research © 2016 American Chemical Society. This is the author created version of a work that has been peer reviewed and accepted for publication by Journal of Proteome Research, American Chemical Society. It incorporates referee’s comments but changes resulting from the publishing process, such as copyediting, structural formatting, may not be reflected in this document. The published version is available at: [http://dx.doi.org/10.1021/acs.jproteome.6b00748]. 47 p. application/pdf
institution Nanyang Technological University
building NTU Library
continent Asia
country Singapore
Singapore
content_provider NTU Library
collection DR-NTU
language English
topic SILAC mass spectrometry
Secretome
spellingShingle SILAC mass spectrometry
Secretome
Zhang, Songjing
Weng, Ting
Cheruba, Elsie
Guo, Tiannan
Chan, Hei
Sze, Siu Kwan
Koh, Cheng-Gee
Phosphatase POPX2 Exhibits Dual Regulatory Functions in Cancer Metastasis
description 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.
author2 School of Biological Sciences
author_facet School of Biological Sciences
Zhang, Songjing
Weng, Ting
Cheruba, Elsie
Guo, Tiannan
Chan, Hei
Sze, Siu Kwan
Koh, Cheng-Gee
format Article
author Zhang, Songjing
Weng, Ting
Cheruba, Elsie
Guo, Tiannan
Chan, Hei
Sze, Siu Kwan
Koh, Cheng-Gee
author_sort Zhang, Songjing
title Phosphatase POPX2 Exhibits Dual Regulatory Functions in Cancer Metastasis
title_short Phosphatase POPX2 Exhibits Dual Regulatory Functions in Cancer Metastasis
title_full Phosphatase POPX2 Exhibits Dual Regulatory Functions in Cancer Metastasis
title_fullStr Phosphatase POPX2 Exhibits Dual Regulatory Functions in Cancer Metastasis
title_full_unstemmed Phosphatase POPX2 Exhibits Dual Regulatory Functions in Cancer Metastasis
title_sort phosphatase popx2 exhibits dual regulatory functions in cancer metastasis
publishDate 2017
url https://hdl.handle.net/10356/82297
http://hdl.handle.net/10220/43514
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