3 research outputs found
Integrative Transcriptome and Proteome Study to Identify the Signaling Network Regulated by POPX2 Phosphatase
POPX2 is a serine/threonine phosphatase
belonging to the protein
phosphatase 2C (PP2C) family that has been found to be elevated in
invasive breast cancer cells. Silencing of POPX2 results in lower
cell motility and invasiveness. The molecular mechanism of POPX2-regulated
cell motility is not well understood. To identify the relevant signaling
pathways, we investigated the transcriptome and proteome of POPX2-knockdown
MDA-MB-231 breast cancer cells. Our data suggest that POPX2 might
be involved in the regulation of focal adhesions and cytoskeleton
dynamics through the regulation of MAP kinase (MAPK1/3) and glycogen
synthase kinase 3 (GSK3α/β) activities. Silencing POPX2
alters phosphorylation levels of MAPK1/3 and GSK3α/β and
results in reduced activity of these kinases. Both MAPK and GSK3 are
known to regulate the activities of transcription factors. MAPK1/3
are also implicated in the phosphorylation of stathmin. The level
of phospho-stathmin was found to be lower in POPX2 knockdown cells.
As phosphorylation of stathmin inhibits its microtubule severing activity,
we observed less stable microtubules in POPX2 knockdown cells. Taken
together, our data suggest that POPX2 might regulate cell motility
through its regulation of the MAPK1/3, leading to changes in the cytoskeleton
and cell motility
Integrative Transcriptome and Proteome Study to Identify the Signaling Network Regulated by POPX2 Phosphatase
POPX2 is a serine/threonine phosphatase
belonging to the protein
phosphatase 2C (PP2C) family that has been found to be elevated in
invasive breast cancer cells. Silencing of POPX2 results in lower
cell motility and invasiveness. The molecular mechanism of POPX2-regulated
cell motility is not well understood. To identify the relevant signaling
pathways, we investigated the transcriptome and proteome of POPX2-knockdown
MDA-MB-231 breast cancer cells. Our data suggest that POPX2 might
be involved in the regulation of focal adhesions and cytoskeleton
dynamics through the regulation of MAP kinase (MAPK1/3) and glycogen
synthase kinase 3 (GSK3α/β) activities. Silencing POPX2
alters phosphorylation levels of MAPK1/3 and GSK3α/β and
results in reduced activity of these kinases. Both MAPK and GSK3 are
known to regulate the activities of transcription factors. MAPK1/3
are also implicated in the phosphorylation of stathmin. The level
of phospho-stathmin was found to be lower in POPX2 knockdown cells.
As phosphorylation of stathmin inhibits its microtubule severing activity,
we observed less stable microtubules in POPX2 knockdown cells. Taken
together, our data suggest that POPX2 might regulate cell motility
through its regulation of the MAPK1/3, leading to changes in the cytoskeleton
and cell motility
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