FSIP1 regulates autophagy in breast cancer.

Abstract

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.

• Authors: Caigang Liu, Lisha Sun, Jie Yang, Tong Liu, Yongliang Yang, Se-Min Kim, Xunyan Ou, Yining Wang, Li Sun, Mone Zaidi, Maria I New, Tony Yuen, Qiyong Guo
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 115 Issue 51 Pg. 13075-13080 (12 18 2018) ISSN: 1091-6490 [Electronic] United States
• PMID: 30509973 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Carrier Proteins
• FSIP1 protein, human
• Seminal Plasma Proteins
• AMP-Activated Protein Kinases

Topics

• AMP-Activated Protein Kinases (genetics, metabolism)
• Antineoplastic Agents (pharmacology)
• Autophagy
• Carrier Proteins (genetics, metabolism)
• Cell Movement
• Cell Proliferation
• Drug Resistance, Neoplasm
• Female
• Humans
• Neoplasm Invasiveness
• Seminal Plasma Proteins (genetics, metabolism)
• Triple Negative Breast Neoplasms (genetics, metabolism, pathology)
• Tumor Cells, Cultured