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REVIEW

SLUG: Critical regulator of epithelial cell identity in breast development and cancer

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Pages 578-587 | Received 18 Jun 2014, Accepted 09 Aug 2014, Published online: 26 Jan 2015

Figures & data

Figure 1. Schematic diagram of the main functional domains of the SNAIL (SNAI1) and SLUG (SNAI2) proteins. The common domains include the N-terminal SNAG domain and C-terminal zinc finger domains. NES, nuclear export sequence.

Figure 1. Schematic diagram of the main functional domains of the SNAIL (SNAI1) and SLUG (SNAI2) proteins. The common domains include the N-terminal SNAG domain and C-terminal zinc finger domains. NES, nuclear export sequence.

Figure 2. Cellular components of the mammary epithelium. (A) Cross section of a bilayered duct. Luminal cells line the inner duct lumen and are surrounded by an outer layer of contractile basal cells. (B) Flow cytometry plots of primary human mammary epithelial cells analyzed for expression of (i) EPCAM vs. CD49f and (ii) CD24 vs. CD49f expression. Mature luminal, luminal progenitor, and basal/stem populations are indicated.

Figure 2. Cellular components of the mammary epithelium. (A) Cross section of a bilayered duct. Luminal cells line the inner duct lumen and are surrounded by an outer layer of contractile basal cells. (B) Flow cytometry plots of primary human mammary epithelial cells analyzed for expression of (i) EPCAM vs. CD49f and (ii) CD24 vs. CD49f expression. Mature luminal, luminal progenitor, and basal/stem populations are indicated.

Figure 3. SLUG is a Regulator of Mammary Epithelial Cell-State Dynamics. Schematic diagrams outlining the various functions of SLUG in mammary epithelial cells. (A) SLUG regulates MEC differentiation. As a transcriptional repressor, SLUG represses transcription of luminal lineage genes and maintains cells in a basal/progenitor-like state. (B) During tissue regeneration following transplantation and tumor initiation, SLUG may be necessary for lineage-restricted cells to de-differentiate into a more primitive, stem-like state. (C) SLUG cooperates with SOX9 to promote the mammary stem cell state. (D) SLUG regulates stochastic cell-state transitions between luminal, basal, and stem cells. Following SLUG knockdown, there are decreased transitions into the basal state and increased transitions into the luminal state. SLUG KD also affects transition into and out of the stem cell state. (E) SLUG promotes the EMT.

Figure 3. SLUG is a Regulator of Mammary Epithelial Cell-State Dynamics. Schematic diagrams outlining the various functions of SLUG in mammary epithelial cells. (A) SLUG regulates MEC differentiation. As a transcriptional repressor, SLUG represses transcription of luminal lineage genes and maintains cells in a basal/progenitor-like state. (B) During tissue regeneration following transplantation and tumor initiation, SLUG may be necessary for lineage-restricted cells to de-differentiate into a more primitive, stem-like state. (C) SLUG cooperates with SOX9 to promote the mammary stem cell state. (D) SLUG regulates stochastic cell-state transitions between luminal, basal, and stem cells. Following SLUG knockdown, there are decreased transitions into the basal state and increased transitions into the luminal state. SLUG KD also affects transition into and out of the stem cell state. (E) SLUG promotes the EMT.

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