1. GATA3 targets semaphorin 3B in mammary epithelial cells to suppress breast cancer progression and metastasis
- Author
-
Shahi, P, Wang, C-Y, Chou, J, Hagerling, C, Gonzalez Velozo, H, Ruderisch, A, Yu, Y, Lai, M-D, and Werb, Z
- Subjects
Biochemistry and Cell Biology ,Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Biological Sciences ,Cancer ,Breast Cancer ,Aetiology ,2.1 Biological and endogenous factors ,Animals ,Breast ,Breast Neoplasms ,Cell Line ,Tumor ,Cell Movement ,Cell Proliferation ,Disease Progression ,Epithelial Cells ,Female ,GATA3 Transcription Factor ,Gene Expression Regulation ,Neoplastic ,Lim Kinases ,Membrane Glycoproteins ,Mice ,Nude ,Neoplasm Metastasis ,Prognosis ,Semaphorins ,Signal Transduction ,Tumor Suppressor Proteins ,Clinical Sciences ,Oncology & Carcinogenesis ,Biochemistry and cell biology ,Oncology and carcinogenesis - Abstract
Semaphorin 3B (SEMA3B) is a secreted axonal guidance molecule that is expressed during development and throughout adulthood. Recently, SEMA3B has emerged as a tumor suppressor in non-neuronal cells. Here, we show that SEMA3B is a direct target of GATA3 transcriptional activity. GATA3 is a key transcription factor that regulates genes involved in mammary luminal cell differentiation and tumor suppression. We show that GATA3 relies on SEMA3B for suppression of tumor growth. Loss of SEMA3B renders GATA3 inactive and promotes aggressive breast cancer development. Overexpression of SEMA3B in cells lacking GATA3 induces a GATA3-like phenotype and higher levels of SEMA3B are associated with better cancer patient prognosis. Moreover, SEMA3B interferes with activation of LIM kinases (LIMK1 and LIMK2) to abrogate breast cancer progression. Our data provide new insights into the role of SEMA3B in mammary gland and provides a new branch of GATA3 signaling that is pivotal for inhibition of breast cancer progression and metastasis.
- Published
- 2017