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.