Abstract:
:Epithelial-to-mesenchymal transition (EMT), marked by the dissolution of cell-cell junctions, loss of cell polarity and increased cell motility, is one of the essential steps for prostate cancer metastasis. However, the underlying mechanism has not been fully explored. We report in this study that Shp2 is upregulated in prostate cancers and is associated with a poor disease outcome, namely tumor metastasis and shortened patient survival. Overexpression of wild-type Shp2 or an oncogenic Shp2 mutant leads to increased prostate cancer cell proliferation, colony and sphere formation, and in vivo tumor formation. Opposite effects are seen in Shp2-knockdown cells. Moreover, Shp2 promotes in vitro migration and in vivo metastasis of prostatic tumor cells. Mechanistically, Shp2 interacts with PAR3 (partitioning-defective 3) via its Src homology-2 domain. Ectopic expression of Shp2 attenuates the phosphorylation of PAR3 and the formation of the PAR3/PAR6/atypical protein kinase C polarity protein complex, resulting in disrupted cell polarity, dysregulated cell-cell junctions and increased EMT. These findings provide a novel mechanism by which oncogenic signal-transduction molecules regulate cell polarity and induction of EMT.
journal_name
Oncogenejournal_title
Oncogeneauthors
Zhang K,Zhao H,Ji Z,Zhang C,Zhou P,Wang L,Chen Q,Wang J,Zhang P,Chen Z,Zhu HH,Gao WQdoi
10.1038/onc.2015.184subject
Has Abstractpub_date
2016-03-10 00:00:00pages
1271-82issue
10eissn
0950-9232issn
1476-5594pii
onc2015184journal_volume
35pub_type
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