CD151 Represses Mammary Gland Development by Maintaining the Niches of Progenitor Cells

Authors

Yuanqin Yin, University of Kentucky
Xinyu Deng, University of Kentucky
Zeyi Liu, University of Kentucky
Lauren A. Baldwin, University of KentuckyFollow
Jason R. Lefringhouse, University of KentuckyFollow
Jiayang Zhang, University of Kentucky
John T Hoff, University of Kentucky
Sonia F. Erfani, University of KentuckyFollow
Edmund B. Rucker III, University of KentuckyFollow
Kathleen L. O'Connor, University of KentuckyFollow
Chunming Liu, University of KentuckyFollow
Yadi Wu, University of KentuckyFollow
Binhua P. Zhou, University of KentuckyFollow
Xiuwei H. Yang, University of KentuckyFollow

Abstract

Tetraspanin CD151 interacts with laminin-binding integrins (i.e., α3β1, α6β1 and α6β4) and other cell surface molecules to control diverse cellular and physiological processes, ranging from cell adhesion, migration and survival to tissue architecture and homeostasis. Here, we report a novel role of CD151 in maintaining the branching morphogenesis and activity of progenitor cells during the pubertal development of mammary glands. In contrast to the disruption of laminin-binding integrins, CD151 removal in mice enhanced the tertiary branching in mammary glands by 2.4-fold and the number of terminal end buds (TEBs) by 30%, while having minimal influence on either primary or secondary ductal branching. Consistent with these morphological changes are the skewed distribution of basal/myoepithelial cells and a 3.2-fold increase in proliferating Ki67-positive cells. These novel observations suggest that CD151 impacts the branching morphogenesis of mammary glands by upregulating the activities of bipotent progenitor cells. Indeed, our subsequent analyses indicate that upon CD151 removal the proportion of CD24^HiCD49f^Lowprogenitor cells in the mammary gland increased by 34%, and their proliferating and differentiating activities were significantly upregulated. Importantly, fibronectin, a pro-branching extracellular matrix (ECM) protein deposited underlying mammary epithelial or progenitor cells, increased by >7.2-fold. Moreover, there was a concomitant increase in the expression and nuclear distribution of Slug, a transcription factor implicated in the maintenance of mammary progenitor cell activities. Taken together, our studies demonstrate that integrin-associated CD151 represses mammary branching morphogenesis by controlling progenitor cell activities, ECM integrity and transcription program.

Document Type

Article

Publication Date

9-1-2014

Notes/Citation Information

Published in Cell Cycle, v. 13, issue 17, p. 2707-2722.

© 2014 Taylor & Francis Group, LLC

Digital Object Identifier (DOI)

https://doi.org/10.4161/15384101.2015.945823

Funding Information

This study was supported in part through DOD Award (W81XWH-07–1–0568), Susan G. Komen For The Cure Career Catalyst Award (KG081481), NIH COBRE/pilot project fund and pilot study award from the American Cancer Society (IRG 85–001–25) to X. H. Yang, RO1 (CA125454) to B. P. Zhou, and R01 (CA109136) to K. L. O'Connor.

Repository Citation

Yin, Yuanqin; Deng, Xinyu; Liu, Zeyi; Baldwin, Lauren A.; Lefringhouse, Jason R.; Zhang, Jiayang; Hoff, John T; Erfani, Sonia F.; Rucker, Edmund B. III; O'Connor, Kathleen L.; Liu, Chunming; Wu, Yadi; Zhou, Binhua P.; and Yang, Xiuwei H., "CD151 Represses Mammary Gland Development by Maintaining the Niches of Progenitor Cells" (2014). Molecular and Cellular Biochemistry Faculty Publications. 150.
https://uknowledge.uky.edu/biochem_facpub/150