Tumor suppressor FRMD3 controls mammary epithelial cell fate determination via notch signaling pathway

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	Tumor suppressor FRMD3 controls mammary epithelial cell fate determination via notch signaling pathway
	Ma, J; Gong, YQ; Sun, XR; Liu, C; Li, XY; Sun, Y; Yang, DC; He, JM; Wang, MY; Du, J; Zhang, J; Xu, WZ; Wang, TZ; Chi, XC; Tang, Y; Song, JG; Wang, YL; Ma, F; Chen, CS; Zhang, HQ; Zhan, J
	2024
发表期刊	SCIENCE ADVANCES
ISSN	2375-2548
卷号	10 期号:27
摘要	The luminal-to-basal transition in mammary epithelial cells (MECs) is accompanied by changes in epithelial cell lineage plasticity; however, the underlying mechanism remains elusive. Here, we report that deficiency of Frmd3 inhibits mammary gland lineage development and induces stemness of MECs, subsequently leading to the occurrence of triple-negative breast cancer. Loss of Frmd3 in PyMT mice results in a luminal-to-basal transition phenotype. Single-cell RNA sequencing of MECs indicated that knockout of Frmd3 inhibits the Notch signaling pathway. Mechanistically, FERM domain-containing protein 3 (FRMD3) promotes the degradation of Disheveled-2 by disrupting its interaction with deubiquitinase USP9x. FRMD3 also interrupts the interaction of Disheveled-2 with CK1, FOXK1/2, and NICD and decreases Disheveled-2 phosphorylation and nuclear localization, thereby impairing Notch-dependent luminal epithelial lineage plasticity in MECs. A low level of FRMD3 predicts poor outcomes for breast cancer patients. Together, we demonstrated that FRMD3 is a tumor suppressor that functions as an endogenous activator of the Notch signaling pathway, facilitating the basal-to-luminal transformation in MECs.
收录类别	sci
语种	英语
文献类型	期刊论文
条目标识符	http://ir.kiz.ac.cn/handle/152453/14226
专题	科研部门_肿瘤生物学（陈策实）
推荐引用方式 GB/T 7714	Ma, J,Gong, YQ,Sun, XR,et al. Tumor suppressor FRMD3 controls mammary epithelial cell fate determination via notch signaling pathway[J]. SCIENCE ADVANCES,2024,10(27).
APA	Ma, J.,Gong, YQ.,Sun, XR.,Liu, C.,Li, XY.,...&Zhan, J.(2024).Tumor suppressor FRMD3 controls mammary epithelial cell fate determination via notch signaling pathway.SCIENCE ADVANCES,10(27).
MLA	Ma, J,et al."Tumor suppressor FRMD3 controls mammary epithelial cell fate determination via notch signaling pathway".SCIENCE ADVANCES 10.27(2024).

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