FLOT1 promotes gastric cancer progression and metastasis through BCAR1/ERK signaling

Ran Wang; Wei Huang; Kaimei Cai; Shihan Xiao; Wuming Zhang; Xianqin Hu; Jianping Guo; Linfeng Mao; Weijie Yuan; Yi Xu; Zihua Chen; Zhikang Chen; Chen Lai

doi:10.7150/ijbs.82606

FLOT1 promotes gastric cancer progression and metastasis through BCAR1/ERK signaling

Int J Biol Sci. 2023 Oct 2;19(16):5104-5119. doi: 10.7150/ijbs.82606. eCollection 2023.

Authors

Ran Wang^{1

2

3}, Wei Huang⁴, Kaimei Cai^{2

3}, Shihan Xiao⁵, Wuming Zhang^{1

2}, Xianqin Hu^{1

2}, Jianping Guo⁶, Linfeng Mao⁷, Weijie Yuan^{1

2

3

8}, Yi Xu^{2

3}, Zihua Chen^{1

2

3

8}, Zhikang Chen^{1

2

3

8}, Chen Lai^{1

2

3

8}

Affiliations

¹ Department of General Surgery, Xiangya Hospital, Central South University, Changsha,410008, Hunan Province, China.
² Hunan Key Laboratory of Precise Diagnosis and Treatment of Gastrointestinal Tumor, Xiangya Hospital, Central South University, Changsha,410008, Hunan Province, China.
³ National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha,410008, Hunan Province, China.
⁴ Research Center of Carcinogenesis and Targeted Therapy, Xiangya Hospital, Central South University, Changsha, 410008, Hunan Province, China.
⁵ Department of Breast and Thyroid Surgery, Tongji Medical College, Union Hospital, Huazhong University of Science and Technology, Wuhan, 430000, Hubei Province, China.
⁶ Department of Gastrointestinal Surgery, the Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510000, Guangdong Province, China.
⁷ Department of Hepatobiliary Surgery, The First Affiliated Hospital of GuangXi Medical University, Nanning, 530021, Guangxi Province, China.
⁸ International Joint Research Center of Minimally Invasive Endoscopic Technology Equipment & Standardization, Xiangya Hospital, Central South University, Changsha,410000, Hunan Province, China.

Abstract

Flotillin-1 (FLOT1) is a member of the flotillin family and serves as a hallmark of lipid rafts involved in the process of signaling transduction and vesicular trafficking. Here, we find FLOT1 promotes gastric cancer cell progression and metastasis by interacting with BCAR1, through ERK signaling. FLOT1 regulates BCAR1 phosphorylation and translocation. Overexpression of FLOT1 increases, while knockdown of FLOT1 decreases gastric cancer cell proliferation, migration and invasion. BCAR1 knockdown could block FLOT1 induced gastric cancer cell proliferation, migration and invasion. Re-expression of wildtype rather than mutant BCAR1 (Y410F) could partially restore FLOT1 knockdown induced gastric cancer cell migration and invasion, while the restore could be inhibited by ERK inhibitor. Furthermore, FLOT1 and BCAR1 expression is closely related to gastric cancer patients' poor outcome. Thus, our findings confirm that BCAR1 mediates FLOT1 induced gastric cancer progression and metastasis through ERK signaling, which may provide a novel pathway for gastric cancer treatment.

Keywords: BCAR1; FLOT1; gastric cancer; metastasis; progression.

Publication types

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

MeSH terms

Cell Line, Tumor
Crk-Associated Substrate Protein / metabolism
Humans
Membrane Proteins / metabolism
Signal Transduction / genetics
Stomach Neoplasms* / genetics

Substances

flotillins
Membrane Proteins
BCAR1 protein, human
Crk-Associated Substrate Protein