FSIP1 regulates autophagy in breast cancer
Menée sur des lignées cellulaires de cancer mammaire triplement négatif et à l'aide d'une xénogreffe sur un modèle murin, cette étude met en évidence le rôle de la protéine FSIP1 dans la prolifération, l'invasion et l'autophagie des cellules cancéreuses
Fibrous sheath interacting protein 1 (FSIP1) has been identified as a poor prognostic indicator of breast cancer. Here, we report that FSIP1 positively regulates the proliferation and invasion of triple-negative breast cancer (TNBC) cells, and its silencing promotes drug resistance by inducing autophagy, by reducing mitochondrial biogenesis, and by enhancing AMP-activated protein kinase activation. Collectively, our findings may aid in the design of therapies for advanced TNBC.Fibrous sheath interacting protein 1 (FSIP1) is a cancer antigen expressed in the majority of breast cancer tissues and is associated with poor prognosis. However, the role of FSIP1 in the progression and drug sensitivity of triple-negative breast cancer (TNBC) has not been explored. Here, we show that FSIP1 deficiency by shRNA-mediated knockdown or CRISPR-Cas9–mediated knockout significantly inhibits the proliferation and invasion of TNBC cells and impairs chemotherapy-induced growth inhibition in vivo. Computational modeling predicted that FSIP1 binds to ULK1, and this was established by coimmunoprecipitation. FSIP1 deficiency promoted autophagy, enhanced AMP-activated protein kinase (AMPK) signaling, and decreased mechanistic target of rapamycin (mTOR) and Wnt/β-catenin activity. In contrast, knockdown of AMPK or inhibition of autophagy restored the sensitivity to chemotherapy drugs in TNBC cells. Our findings uncover a role of FSIP1 as well as mechanisms underlying FSIP1 action in drug sensitivity and may, therefore, aid in design of TNBC therapies.