SHARPIN regulates collagen architecture and ductal outgrowth in the developing mouse mammary gland.
Document Type
Article
Publication Date
1-17-2017
JAX Source
EMBO J 2017 Jan 17; 36(2):165-182
Volume
36
Issue
2
First Page
165
Last Page
182
ISSN
1460-2075
PMID
27974362
Grant
AR049288
Abstract
SHARPIN is a widely expressed multifunctional protein implicated in cancer, inflammation, linear ubiquitination and integrin activity inhibition; however, its contribution to epithelial homeostasis remains poorly understood. Here, we examined the role of SHARPIN in mammary gland development, a process strongly regulated by epithelial-stromal interactions. Mice lacking SHARPIN expression in all cells (Sharpin(cpdm)), and mice with a stromal (S100a4-Cre) deletion of Sharpin, have reduced mammary ductal outgrowth during puberty. In contrast, Sharpin(cpdm) mammary epithelial cells transplanted in vivo into wild-type stroma, fully repopulate the mammary gland fat pad, undergo unperturbed ductal outgrowth and terminal differentiation. Thus, SHARPIN is required in mammary gland stroma during development. Accordingly, stroma adjacent to invading mammary ducts of Sharpin(cpdm) mice displayed reduced collagen arrangement and extracellular matrix (ECM) stiffness. Moreover, Sharpin(cpdm) mammary gland stromal fibroblasts demonstrated defects in collagen fibre assembly, collagen contraction and degradation in vitro Together, these data imply that SHARPIN regulates the normal invasive mammary gland branching morphogenesis in an epithelial cell extrinsic manner by controlling the organisation of the stromal ECM. EMBO J 2017 Jan 17; 36(2):165-182.
Recommended Citation
Peuhu E,
Kaukonen R,
Lerche M,
Saari M,
Guzmán C,
Rantakari P,
De Franceschi N,
Wärri A,
Georgiadou M,
Jacquemet G,
Mattila E,
Virtakoivu R,
Liu Y,
Attieh Y,
Silva K,
Betz T,
Sundberg J,
Salmi M,
Deugnier M,
Eliceiri K,
Ivaska J.
SHARPIN regulates collagen architecture and ductal outgrowth in the developing mouse mammary gland. EMBO J 2017 Jan 17; 36(2):165-182