Knockdown of PC4 increases chemosensitivity of Oxaliplatin in triple negative breast cancer by suppressing mTOR pathway

Qing Wang; Le Ma; Long Chen; Hongdan Chen; Min Luo; Wei Yang; Fengying Liao; Qiang Gong; Yang Wang; Zeyu Yang; Jie Wu; Can Zhang; Jiancheng Zheng; Shiqian Han; Yu Leng; Peng Luo; Chunmeng Shi

doi:10.1016/j.bbrc.2021.01.029

Knockdown of PC4 increases chemosensitivity of Oxaliplatin in triple negative breast cancer by suppressing mTOR pathway

Biochem Biophys Res Commun. 2021 Mar 12:544:65-72. doi: 10.1016/j.bbrc.2021.01.029. Epub 2021 Jan 29.

Authors

Qing Wang¹, Le Ma², Long Chen³, Hongdan Chen⁴, Min Luo⁵, Wei Yang¹, Fengying Liao³, Qiang Gong⁶, Yang Wang³, Zeyu Yang⁴, Jie Wu³, Can Zhang³, Jiancheng Zheng³, Shiqian Han⁷, Yu Leng⁸, Peng Luo⁹, Chunmeng Shi¹⁰

Affiliations

¹ Department of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China; Institute of Rocket Force Medicine, State Key Laboratory of Trauma, Burns and Combined Injury, Third Military Medical University, Chongqing, 400038, China.
² Institute of Rocket Force Medicine, State Key Laboratory of Trauma, Burns and Combined Injury, Third Military Medical University, Chongqing, 400038, China; Department of Hematology, Southwest Hospital, Third Military Medical University, Chongqing, 40038, China.
³ Institute of Rocket Force Medicine, State Key Laboratory of Trauma, Burns and Combined Injury, Third Military Medical University, Chongqing, 400038, China.
⁴ Department of Breast and Thyroid Surgery, Chongqing General Hospital, University of Chinese Academy of Sciences, Chongqing, 401121, China.
⁵ Institute of Rocket Force Medicine, State Key Laboratory of Trauma, Burns and Combined Injury, Third Military Medical University, Chongqing, 400038, China; Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, School of Public Health, Guizhou Medical University, Guiyang, 550025, China.
⁶ Department of Hematology, Southwest Hospital, Third Military Medical University, Chongqing, 40038, China.
⁷ Institute of Tropical Medicine, Third Military Medical University, Chongqing, 400038, China.
⁸ Department of Ophthalmology, The Third Affiliated Hospital of Chongqing Medical University (Gener Hospital), Chongqing, 401120, China.
⁹ Institute of Rocket Force Medicine, State Key Laboratory of Trauma, Burns and Combined Injury, Third Military Medical University, Chongqing, 400038, China. Electronic address: [email protected].
¹⁰ Department of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China; Institute of Rocket Force Medicine, State Key Laboratory of Trauma, Burns and Combined Injury, Third Military Medical University, Chongqing, 400038, China. Electronic address: [email protected].

PMID: 33524870
DOI: 10.1016/j.bbrc.2021.01.029

Abstract

As a multifunctional nuclear protein, the human positive cofactor 4 (PC4) is highly expressed in various tumors including breast cancer and has potential roles in cancer development and progression. However, the functional signatures and molecular mechanisms of PC4 in triple negative breast cancer (TNBC) progression and chemotherapeutic response are still unknown. In this study, we found that PC4 is significantly upregulated in TNBC cells compared with non-TNBC cells, implying its potential role in TNBC. Then, in vivo and in vitro studies revealed that knockdown of PC4 increased chemosensitivity of Oxaliplation (Oxa) in TNBC by suppressing mTOR pathway. Therefore, our findings demonstrated the signatures and molecular mechanisms of PC4 in TNBC chemotherapeutic response, and indicated that PC4 might be a promising therapeutic target for TNBC.

Keywords: Chemosensitivity; Mammalian target of rapamycin; Oxaliplatin; Positive cofactor 4; Triple negative breast cancer.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antineoplastic Agents / pharmacology
Cell Line, Tumor
Cell Proliferation
DNA-Binding Proteins / antagonists & inhibitors*
DNA-Binding Proteins / genetics
DNA-Binding Proteins / metabolism
Drug Resistance, Neoplasm*
Female
Gene Knockdown Techniques / methods*
Humans
Mice
Mice, Nude
Oxaliplatin / pharmacology*
Phosphorylation
Signal Transduction
TOR Serine-Threonine Kinases / antagonists & inhibitors*
Transcription Factors / antagonists & inhibitors*
Transcription Factors / genetics
Transcription Factors / metabolism
Triple Negative Breast Neoplasms / drug therapy*
Triple Negative Breast Neoplasms / metabolism
Triple Negative Breast Neoplasms / pathology
Up-Regulation

Substances

Antineoplastic Agents
DNA-Binding Proteins
SUB1 protein, human
Transcription Factors
Oxaliplatin
MTOR protein, human
TOR Serine-Threonine Kinases