FHL2 activates β-catenin/Wnt signaling by complexing with APC and TRIM63 in lung adenocarcinoma

Jian Gao; Yong-Qiang Ao; Jie Deng; Miao Lin; Shuai Wang; Jia-Hao Jiang; Jian-Yong Ding

Translational Oncology (Dec 2024)

FHL2 activates β-catenin/Wnt signaling by complexing with APC and TRIM63 in lung adenocarcinoma

Jian Gao,
Yong-Qiang Ao,
Jie Deng,
Miao Lin,
Shuai Wang,
Jia-Hao Jiang,
Jian-Yong Ding

Affiliations

Jian Gao: Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China; Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China
Yong-Qiang Ao: Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China; Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China
Jie Deng: Institute of Vascular Disease, Shanghai TCM-Integrated Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
Miao Lin: Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China; Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China
Shuai Wang: Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China; Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China
Jia-Hao Jiang: Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China; Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China; Corresponding authors at: Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, China, 200032.
Jian-Yong Ding: Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China; Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China; Corresponding authors at: Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, China, 200032.

Journal volume & issue: Vol. 50
p. 102131

Abstract

Read online

Objectives: Four and a half LIM domain 2 protein (FHL2) was reported to regulate the progression of various cancers and this study aimed to clarify the intrinsic mechanism of FHL2 facilitating the progression of lung adenocarcinoma. Methods: In this study, bioinformatic analysis and immunohistochemistry staining were used to confirm the FHL2 levels in patients with lung adenocarcinoma. The potential influence of FHL2 on the biological function of lung adenocarcinoma cells was verified in vitro and in vivo. To uncover the potential mechanism contributing to the advance of lung adenocarcinoma, liquid chromatography‒mass spectrometry and immunoprecipitation assays were performed to detect the partners of FHL2. Results: FHL2 levels were upregulated in lung adenocarcinoma and contributed to a dismal prognosis. Moreover, in vitro and in vivo assays suggested that genetic inhibition of FHL2 undermined the viability, migration and invasion of lung adenocarcinoma cells, while forced expression of FHL2 showed the opposite trend. Mechanistically, liquid chromatography‒mass spectrometry and coimmunoprecipitation assays revealed that FHL2 could function as a scaffold to enhance TRIM63-mediated ubiquitination of APC. The degradation of APC further stabilized β-catenin and activated Wnt signaling pathway. Conclusion: Collectively, this study uncovered the underlying mechanism by which FHL2 regulates the biological characteristics of tumors and provided a novel target for lung adenocarcinoma treatment.

Published in Translational Oncology

ISSN: 1944-7124 (Print); 1936-5233 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Internal medicine: Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Website: https://www.journals.elsevier.com/translational-oncology/

About the journal

Abstract

Keywords