title: Opposite regulation of epithelial-to-mesenchymal transition and cell invasiveness by periostin between prostate and bladder cancer cells.
abstract: We previously showed that periostin expression is downregulated in human bladder cancer tissues and that ectopic expression of periostin suppresses the invasiveness of bladder cancer cells. However, in most other human cancers studied, the expression of periostin promotes cell invasiveness. In the present study, we investigated the regulation of the epithelial-to-mesenchymal transition (EMT) and cell invasiveness by periostin in bladder and prostate cancer cell lines, and found opposite regulation of EMT and cell invasiveness by periostin. Periostin upregulated E-cadherin expression in bladder cancer cells but downregulated it in prostate cancer cells. Periostin suppressed cell invasiveness in bladder cancer cells but promoted it in prostate cancer cells. Snail, a negative regulator of E-cadherin, was upregulated by periostin in prostate cancer cells, while Twist, another negative regulator of E-cadherin, was downregulated in bladder cancer cells. The C-terminal region of periostin was sufficient for these functions in bladder cancer cells but not in prostate cancer cells. Knockdown of endogenous Snail by siRNA suppressed cell invasiveness in prostate cancer cells expressing periostin. Periostin also suppressed Akt phosphorylation in bladder cancer cells but enhanced it in prostate cancer cells. Treatment with Akt inhibitor increased E-cadherin expression and suppressed both Twist expression and cell invasiveness of bladder cancer cells. These results indicate that Akt signaling plays a role in the cell-type-dependent regulation of E-cadherin expression and cell invasiveness by periostin via Snail and Twist.
authors.affiliation: Department of Urology, Kohka Public Hospital, 3-39 Rokushin, Kohka, Shiga 528-0014, Japan.
authors.forename: Chul Jang
authors.initials: CJ
authors.lastname: Kim
authors.forename: Kanami
authors.initials: K
authors.lastname: Sakamoto
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Tambe
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Inoue
mesh_terms: D000818:Animals; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D054337:Cell Dedifferentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000235:genetics; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D051379:Mice; D041681:NIH 3T3 Cells; D009361:Neoplasm Invasiveness / Q000235:genetics; D010766:Phosphorylation / Q000187:drug effects; D011471:Prostatic Neoplasms / Q000235:genetics / Q000473:pathology*; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D001749:Urinary Bladder Neoplasms / Q000235:genetics / Q000473:pathology*
chemical_list: D015820:Cadherins; D015815:Cell Adhesion Molecules; C512835:POSTN protein, human; D034741:RNA, Small Interfering; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D051057:Proto-Oncogene Proteins c-akt