Abstract

The pathogenesis of lung cancer, the most common cancer, is complex and unclear, leading to limited treatment options and poor prognosis. To provide molecular insights into lung cancer development, we investigated the function and underlying mechanism of SH2B3 in the regulation of lung cancer. We indicated SH2B3 was diminished while TGF-β1 was elevated in lung cancer tissues and cells. Low SH2B3 level was correlated with poor prognosis of lung cancer patients. SH2B3 overexpression suppressed cancer cell anoikis resistance, proliferation, migration, invasion, and EMT, while TGF-β1 promoted those processes via reducing SH2B3. SH2B3 bound to JAK2 and SHP2 to repress JAK2/STAT3 and SHP2/Grb2/PI3K/AKT signaling pathways, respectively, resulting in reduced cancer cell anoikis resistance, proliferation, migration, invasion, and EMT. Overexpression of SH2B3 suppressed lung cancer growth and metastasis in vivo. In conclusion, SH2B3 restrained the development of anoikis resistance and EMT of lung cancer cells via suppressing JAK2/STAT3 and SHP2/Grb2/PI3K/AKT signaling cascades, leading to decreased cancer cell proliferation, migration, and invasion.

Details

Title
TGF-β1/SH2B3 axis regulates anoikis resistance and EMT of lung cancer cells by modulating JAK2/STAT3 and SHP2/Grb2 signaling pathways
Author
Li-Na, Wang 1 ; Zi-Teng, Zhang 2 ; Wang, Li 3 ; Hai-Xiang, Wei 2 ; Zhang, Tao 2 ; Li-Ming, Zhang 2 ; Lin, Hang 4 ; Zhang, Heng 5   VIAFID ORCID Logo  ; Shao-Qiang, Wang 2   VIAFID ORCID Logo 

1  Affiliated Hospital of Jining Medical University, Jining Medical University, Department of Thoracic Surgery, Jining, P. R. China (GRID:grid.449428.7) (ISNI:0000 0004 1797 7280); Affiliated Hospital of Jining Medical University, Jining Medical University, Medical Research Center, Jining, P. R. China (GRID:grid.449428.7) (ISNI:0000 0004 1797 7280) 
2  Affiliated Hospital of Jining Medical University, Jining Medical University, Department of Thoracic Surgery, Jining, P. R. China (GRID:grid.449428.7) (ISNI:0000 0004 1797 7280) 
3  The Second Xiangya Hospital of Central South University, Department of Thoracic Surgery, Changsha, P. R. China (GRID:grid.452708.c) (ISNI:0000 0004 1803 0208); The Second Xiangya Hospital of Central South University, Hunan Key Laboratory of Early Diagnosis and Precise Treatment of Lung Cancer, Changsha, P. R. China (GRID:grid.452708.c) (ISNI:0000 0004 1803 0208) 
4  Xiangya Hospital, Central South University, Department of General Thoracic Surgery, Changsha, P. R. China (GRID:grid.452223.0) (ISNI:0000 0004 1757 7615) 
5  Xiangya Hospital, Central South University, Department of General Thoracic Surgery, Changsha, P. R. China (GRID:grid.452223.0) (ISNI:0000 0004 1757 7615); Central South University, Xiangya Lung Cancer Center, Xiangya Hospital, Changsha, P. R. China (GRID:grid.216417.7) (ISNI:0000 0001 0379 7164); Hunan Engineering Research Center for Pulmonary Nodules Precise Diagnosis & Treatment, Changsha, P. R. China (GRID:grid.216417.7); National Clinical Research Center for Geriatric Disorders (Xiangya Hospital), Changsha, P. R. China (GRID:grid.452223.0) (ISNI:0000 0004 1757 7615) 
Publication year
2022
Publication date
May 2022
Publisher
Springer Nature B.V.
e-ISSN
20414889
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41419-022-04890-x
ProQuest document ID
2666705911
Copyright
© The Author(s) 2022. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.