Article

Slug/SNAI2 regulates cell proliferation and invasiveness of metastatic prostate cancer cell lines. Tumour Biol

Department of Genetics, Faculty of Basic Sciences, Tarbiat Modares University, Tehran, Iran.
Tumor Biology (Impact Factor: 3.61). 08/2010; 31(4):297-307. DOI: 10.1007/s13277-010-0037-5
Source: PubMed

ABSTRACT 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.

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    • "Several strides have been carried out to identify the factors contributing to EMT in PCa. Transforming growth factor beta (Zhu & Kyprianou 2010), nicotinamide adenine dinucleotide-dependent histone deacetylase or SIRT1 (Byles et al. 2012), platelet-derived growth factor (Kong et al. 2009), TMPRSS2/ERG (Leshem et al. 2011), SNAI2 (SLUG) (Emadi Baygi et al. 2010), DAB2IP (Xie et al. 2010), Hsp27 (HSPB1) (Shiota et al. 2013), and miRNAs (Ru et al. 2012) have all been identified as EMT regulators in PCa. "
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    • "Snail proteins, together with other core EMT/neural crest regulatory factors, are implicated in epithelial plasticity and EMT-like processes during tumor progression [10], [11]. Snai1 expression, and features of EMT have been observed in breast, prostate, lung, ovarian, melanoma, colon and esophageal cancers [12], [13], [14], [15], [16], [17], [18]. Introduction of Snail factors into epithelial tumors results in cells that can disseminate from the primary tumor, are resistant to apoptosis, radiotherapy and chemotherapy, evade immune recognition, and exhibit markers of stem cells [19], [20], [21], [22]. "
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