The skinny on slug

Abstract

The zinc finger transcription factor Slug (Snai2) serves a wide variety of functions in the epidermis, with roles in skin development, hair growth, wound healing, skin cancer, and sunburn. Slug is expressed in basal keratinocytes and hair follicles where it is important in maintaining epidermal homeostasis. Slug also helps coordinate the skin response to exogenous stimuli. Slug is rapidly induced by a variety of growth factors and injurious agents and Slug controls, directly or indirectly, a variety of keratinocyte responses, including changes in differentiation, adhesion, motility, and production of inflammatory mediators. Slug thus modulates the interactions of the keratinocyte with its environment and with surrounding cells. The function of Slug in the epidermis appears to be distinct from that of the closely related Snail transcription factor.

High Motility of Triple-negative Breast Cancer Cells Is Due to Repression of Plakoglobin Gene by Metastasis Modulator Protein SLUG

“…The transcriptional repressor protein SLUG is implicated in several key aspects of metastasis in the epithelial cancer cells (7)(8)(9). It is shown to participate in epithelial to mesenchymal transition through the repression of the cell-cell adhesion molecule E-cadherin (11).…”

“…The genetic and molecular basis for this incidence and the biological basis for the aggressiveness of TNBCs are largely unknown and of high priority (3)(4)(5)(6). The transcription factor SLUG, which controls epithelial to mesenchymal transition, stem cell phenotypes, and therapeutic responsiveness (7)(8)(9), is highly expressed in the highly aggressive basal and mesenchymal subtypes of the TNBC cells (1,10), making it a candidate master regulator of the TNBC phenotype. The uncanny ability of the TNBC cells to metastasize to other vital tissues and organs causes severe pain and mortality in the TNBC patients (3)(4)(5)(6).…”

“…SLUG, also known as SNAI2, is a member of the SNAI superfamily of zinc finger transcriptional repressors (7)(8)(9). It is a C 2 H 2 -type zinc finger transcription factor that binds to E2-box motif (5Ј-CAGGTG-3Ј/5Ј-CACCTG-3Ј) and silences gene expression by chromatin remodeling (7)(8)(9).…”

“…It is a C 2 H 2 -type zinc finger transcription factor that binds to E2-box motif (5Ј-CAGGTG-3Ј/5Ј-CACCTG-3Ј) and silences gene expression by chromatin remodeling (7)(8)(9). SLUG has essential SNAG and SLUG motifs in its repressor domain that mediate its repressor activity (7)(8)(9). SLUG is shown to repress many genes including E-cadherin, BRCA2, cytokeratins, UbE2D3, and vitamin D receptor (11)(12)(13)(14)(15).…”

“…SLUG is reported recently to coordinate with another transcription factor SOX9 and thus to determine the stem cell-ness of aggressive breast cancer cells (16). Although coordinated repression of several cell-cell junction proteins and other associated molecules by SLUG is implicated as the cumulative cause for SLUG-induced invasiveness of breast cancer cells (7)(8)(9), it is not known how dysregulation in SLUG expression increases the motility of these cells.…”