PMID- 30509973
OWN - NLM
STAT- MEDLINE
DCOM- 20190219
LR  - 20200225
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 115
IP  - 51
DP  - 2018 Dec 18
TI  - FSIP1 regulates autophagy in breast cancer.
PG  - 13075-13080
LID - 10.1073/pnas.1809681115 [doi]
AB  - 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/beta-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.
FAU - Liu, Caigang
AU  - Liu C
AD  - Department of Breast Surgery, Shengjing Hospital of China Medical University, 
      Shenyang 110004, China; liucg@sj-hospital.org maria.new@mssm.edu 
      tony.yuen@mssm.edu guoqy@sj-hospital.org.
FAU - Sun, Lisha
AU  - Sun L
AD  - Department of Breast Surgery, Shengjing Hospital of China Medical University, 
      Shenyang 110004, China.
FAU - Yang, Jie
AU  - Yang J
AD  - Department of Breast Surgery, Shengjing Hospital of China Medical University, 
      Shenyang 110004, China.
FAU - Liu, Tong
AU  - Liu T
AD  - Department of Breast Surgery, Shengjing Hospital of China Medical University, 
      Shenyang 110004, China.
FAU - Yang, Yongliang
AU  - Yang Y
AD  - Center for Molecular Medicine, School of Life Science and Biotechnology, Dalian 
      University of Technology, Dalian 116024, China.
FAU - Kim, Se-Min
AU  - Kim SM
AD  - Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 
      10029.
FAU - Ou, Xunyan
AU  - Ou X
AD  - Department of Breast Surgery, Shengjing Hospital of China Medical University, 
      Shenyang 110004, China.
FAU - Wang, Yining
AU  - Wang Y
AD  - Department of Breast Surgery, Shengjing Hospital of China Medical University, 
      Shenyang 110004, China.
FAU - Sun, Li
AU  - Sun L
AD  - Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 
      10029.
FAU - Zaidi, Mone
AU  - Zaidi M
AD  - Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 
      10029.
FAU - New, Maria I
AU  - New MI
AD  - Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY 
      10029; liucg@sj-hospital.org maria.new@mssm.edu tony.yuen@mssm.edu 
      guoqy@sj-hospital.org.
FAU - Yuen, Tony
AU  - Yuen T
AD  - Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 
      10029; liucg@sj-hospital.org maria.new@mssm.edu tony.yuen@mssm.edu 
      guoqy@sj-hospital.org.
FAU - Guo, Qiyong
AU  - Guo Q
AD  - Department of Radiology, Shengjing Hospital of China Medical University, Shenyang 
      110004, China liucg@sj-hospital.org maria.new@mssm.edu tony.yuen@mssm.edu 
      guoqy@sj-hospital.org.
LA  - eng
GR  - R01 AG023176/AG/NIA NIH HHS/United States
GR  - R01 AR065932/AR/NIAMS NIH HHS/United States
GR  - R01 AR067066/AR/NIAMS NIH HHS/United States
GR  - R01 DK113627/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20181203
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Carrier Proteins)
RN  - 0 (FSIP1 protein, human)
RN  - 0 (Seminal Plasma Proteins)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
SB  - IM
MH  - AMP-Activated Protein Kinases/genetics/*metabolism
MH  - Antineoplastic Agents/pharmacology
MH  - *Autophagy
MH  - Carrier Proteins/genetics/*metabolism
MH  - Cell Movement
MH  - Cell Proliferation
MH  - *Drug Resistance, Neoplasm
MH  - Female
MH  - Humans
MH  - Neoplasm Invasiveness
MH  - Seminal Plasma Proteins/genetics/*metabolism
MH  - Triple Negative Breast Neoplasms/genetics/metabolism/*pathology
MH  - Tumor Cells, Cultured
PMC - PMC6304934
OTO - NOTNLM
OT  - AMP-activated protein kinase
OT  - FSIP1 knockdown
OT  - ULK1 serine/threonine protein kinase
OT  - chemoresistance
COIS- The authors declare no conflict of interest.
EDAT- 2018/12/05 06:00
MHDA- 2019/03/21 06:00
PMCR- 2019/06/03
CRDT- 2018/12/05 06:00
PHST- 2018/12/05 06:00 [pubmed]
PHST- 2019/03/21 06:00 [medline]
PHST- 2018/12/05 06:00 [entrez]
PHST- 2019/06/03 00:00 [pmc-release]
AID - 1809681115 [pii]
AID - 201809681 [pii]
AID - 10.1073/pnas.1809681115 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2018 Dec 18;115(51):13075-13080. doi: 
      10.1073/pnas.1809681115. Epub 2018 Dec 3.