CRIPTO/GRP78 Signaling Maintains Fetal and Adult Mammary Stem Cells Ex Vivo

被引：50

作者：

Spike, Benjamin T. ^{[1
]}

Kelber, Jonathan A. ^{[3
]}

Booker, Evan ^{[2
]}

Kalathur, Madhuri ^{[2
]}

Rodewald, Rose ^{[1
]}

Lipianskaya, Julia ^{[1
]}

La, Justin ^{[1
]}

He, Marielle ^{[2
]}

Wright, Tracy ^{[3
]}

Klemke, Richard ^{[3
]}

Wahl, Geoffrey M. ^{[1
]}

Gray, Peter C. ^{[2
]}

机构：

[1] Salk Inst Biol Studies, Gene Express Lab, La Jolla, CA 92037 USA

[2] Salk Inst Biol Studies, Labs Peptide Biol, Clayton Fdn, La Jolla, CA 92037 USA

[3] Univ Calif San Diego, Dept Pathol, La Jolla, CA 92037 USA

来源：

STEM CELL REPORTS | 2014年 / 2卷 / 04期

关键词：

UNFOLDED PROTEIN RESPONSE; GLAND DEVELOPMENT; EPITHELIAL-CELLS; BREAST-CANCER; CRIPTO-1; EXPRESSION; GRP78/BIP; SURFACE; NICHE; PROLIFERATION;

D O I：

10.1016/j.stemcr.2014.02.010

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

Little is known about the extracellular signaling factors that govern mammary stem cell behavior. Here, we identify CRIPTO and its cell-surface receptor GRP78 as regulators of stem cell behavior in isolated fetal and adult mammary epithelial cells. We develop a CRIPTO antagonist that promotes differentiation and reduces self-renewal of mammary stem cell-enriched populations cultured ex vivo. By contrast, CRIPTO treatment maintains the stem cell phenotype in these cultures and yields colonies with enhanced mammary gland reconstitution capacity. Surface expression of GRP78 marks CRIPTO-responsive, stem cell-enriched fetal and adult mammary epithelial cells, and deletion of GRP78 from adult mammary epithelial cells blocks their mammary gland reconstitution potential. Together, these findings identify the CRIPTO/GRP78 pathway as a developmentally conserved regulator of fetal and adult mammary stem cell behavior ex vivo, with implications for the stem-like cells found in many cancers.

引用

页码：427 / 439

页数：13

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