Slug/SNAI2 regulates cell proliferation and invasiveness of metastatic prostate cancer cell lines.
Many metastatic cancers recapitulate the epithelial-to-mesenchymal transition (EMT) resulting in enhanced cell motility and invasiveness. The EMT is regulated by several transcription factors, including the zinc finger protein SNAI2, also named Slug, which appears to exert additional functions during development and cancer progression. We have studied the function of SNAI2 in prostate cancer cells. Quantitative RT-PCR analysis showed strong SNAI2 expression particularly in the PC-3 and PC3-16 prostate carcinoma cell lines. Knockdown of SNAI2 by specific siRNA induced changes in EMT markers and inhibited invasion of both cell lines into a matrigel matrix. SNAI2 siRNA-treated cells did not tolerate detachment from the culture plates, likely at least in part due to downregulation of integrin alpha6beta4. SNAI2 knockdown disturbed the microtubular and actin cytoskeletons, especially severely in PC-3 cells, resulting in grossly enlarged, flattened, and sometimes multinuclear cells. Knockdown also decreased cell proliferation, with a prominent G0/G1 arrest in PC3-16. Together, our data imply that SNAI2 exerts strong effects on the cytoskeleton and adhesion of those prostate cancer cells that express it and is necessary for their proliferation and invasiveness.
Emadi Baygi
Modjtaba
M
Department of Genetics, Faculty of Basic Sciences, Tarbiat Modares University, Tehran, Iran.
Soheili
Zahra-Soheila
ZS
Essmann
Frank
F
Deezagi
Abdolkhaleg
A
Engers
Rainer
R
Goering
Wolfgang
W
Schulz
Wolfgang A
WA
D000199:Actins / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002448:Cell Adhesion; D002453:Cell Cycle; D049109:Cell Proliferation; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000378:metabolism; D020868:Gene Silencing; D006801:Humans; D039161:Integrin alpha6beta4 / Q000378:metabolism; D008297:Male; D009361:Neoplasm Invasiveness; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000502:physiology*; D016335:Zinc Fingers
D000199:Actins; D039161:Integrin alpha6beta4; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C000604407:SNAI1 protein, human; C000604408:SNAI2 protein, human; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors