LGL1 binds to Integrin β1 and inhibits downstream signaling to promote epithelial branching in the mammary gland
| Autor: | Rongze Ma, Difei Gong, Huanyang You, Chongshen Xu, Yunzhe Lu, Gabriele Bergers, Zena Werb, Ophir D. Klein, Claudia K. Petritsch, Pengfei Lu |
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| Rok vydání: | 2022 |
| Předmět: |
extracellular matrix
Medical Physiology Down-Regulation Mice Transgenic collective migration Models Biological General Biochemistry Genetics and Molecular Biology Epithelium Transgenic Mice tumor-suppressor genes Mammary Glands Animal Cell Movement Models Breast Cancer Morphogenesis Animals epithelial polarity Glycoproteins Cell Proliferation integrin signaling Cancer Neoplastic Animal Integrin beta1 Cell Polarity Epithelial Cells Biological Mammary Glands epithelial migration Gene Expression Regulation Neoplastic Gene Expression Regulation Female branching morphogenesis Biochemistry and Cell Biology Signal Transduction Protein Binding |
| Zdroj: | Cell reports, vol 38, iss 7 |
| Popis: | Branching morphogenesis is a fundamental process by which organs in invertebrates and vertebrates form branches to expand their surface areas. The current dogma holds that directional cell migration determines where a new branch forms and thus patterns branching. Here, we asked whether mouse Lgl1, a homolog of the Drosophila tumor suppressor Lgl, regulates epithelial polarity in the mammary gland. Surprisingly, mammary glands lacking Lgl1 have normal epithelial polarity, but they form fewer branches. Moreover, we find that Lgl1 null epithelium is unable to directionally migrate, suggesting that migration is not essential for mammary epithelial branching as expected. We show that LGL1 binds to Integrin β1 and inhibits its downstream signaling, and Integrin β1 overexpression blocks epithelial migration, thus recapitulating the Lgl1 null phenotype. Altogether, we demonstrate that Lgl1 modulation of Integrin β1 signaling is essential for directional migration and that epithelial branching in invertebrates and the mammary gland is fundamentally distinct. |
| Databáze: | OpenAIRE |
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