Snai1 and Snai2 collaborate on tumor growth and metastasis properties of mouse skin carcinoma cell lines

Abstract

Snai1 (Snail) and Snai2 (Slug), the two main members of Snail family factors, are important mediators of epithelial-mesenchymal transitions and involved in tumor progression. We recently reported that Snai1 plays a major role in tumor growth, invasion and metastasis, but the contribution of Snai2 to tumorigenesis is not yet well understood. To approach this question we have silenced Snai2 and/or Snai1 by stable RNA interference in two independent mouse skin carcinoma (HaCa4 and CarB) cell lines. We demonstrate that Snai2 knockdown has a milder effect, but collaborates with Snai1 silencing in reduction of tumor growth potential of either carcinoma cell line when injected into nude mice. Importantly, Snai1 or Snai2 silencing dramatically influences the metastatic ability of squamous carcinoma HaCa4 cells, inducing a strong reduction in liver and lung distant metastasis. However, only Snai1 knockdown has an effective action on invasiveness and fully abolishes tumor cell dissemination into the spleen. These results demonstrate that Snai1 and Snai2 collaborate on primary tumor growth and specifically contribute to site-specific metastasis of HaCa4 cells. These data also indicate that Snai1 is the major regulator of local invasion, supporting a hierarchical participation of both factors in the metastatic process.

Epidermal Snail expression drives skin cancer initiation and progression through enhanced cytoprotection, epidermal stem/progenitor cell expansion and enhanced metastatic potential

“…It was previously demonstrated that Snail knockdown in the squamous carcinoma HaCa4 cell line has a large effect on cellular invasiveness, tumour growth and metastasis. 28 In contrast to BCC, SCC can metastasise in humans. Indeed, in mice with primary SCCs we identified metastatic lung nodules displaying distinct features of skin differentiation.…”

ROCK Cooperated with ET-1 to Induce Epithelial to Mesenchymal Transition through SLUG in Human Ovarian Cancer Cells

“…30) SLUG also induced the expression of some mesenchymal genes, fibronectin. 31) Thus the identification of SLUG as a novel target of ROCK is relevant to understanding EMT mechanisms.…”

Comparative Analysis of Metastasis Variants Derived from Human Prostate Carcinoma Cells

“…17,18 EMT in development and possibly in cancer progression can be mediated by a group of transcription factors (ie, Snail, Slug, and Twist) that, when activated, induce phenotypic changes in cell behavior. 19,20,45,46 These changes involve a loss of polarity and loosening of tight cell-cell junctions, coinciding with decreased levels of functional epithelial markers, especially E-cadherin. A gain of mesenchymal characteristics is also observed, including increased motility and expression of mesenchymal markers (N-cadherin, vimentin, fibronectin).…”