PLAU promotes growth and attenuates cisplatin chemosensitivity in ARID1A-depleted non-small cell lung cancer through interaction with TM4SF1

• Published in: Biology direct 2024-01, Vol.19 (1), p.7-7, Article 7
• Main Authors: Zheng, Yuanliang, Zhang, Lixiang, Zhang, Kangliang, Wu, Shenghao, Wang, Chichao, Huang, Risheng, Liao, Hongli
• Format: Article
• Language: English
• Subjects: AKT protein; Analysis; Animals; Antibodies; ARID1A; Carcinogenesis - genetics; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - pathology; Care and treatment; Cell Line, Tumor; Cell Proliferation; Cells; Chemoresistance; Chromatin; Chromatin remodeling; Cisplatin; Cisplatin - metabolism; Cisplatin - pharmacology; Cisplatin - therapeutic use; Complications and side effects; Depletion; Development and progression; Diagnosis; Drug resistance; Gene expression; Gene Expression Regulation, Neoplastic; Gene sequencing; Genes; Genetic aspects; Growth; Health aspects; Lung cancer; Lung cancer, Non-small cell; Lung cancer, Small cell; Lung Neoplasms - drug therapy; Lung Neoplasms - genetics; Lung Neoplasms - pathology; Mass spectrometry; Mice; Mice, Nude; Mutation; Non-small cell lung carcinoma; Patient outcomes; Phenotypes; Plasmids; PLAU; Proteins; Proto-Oncogene Proteins c-akt - genetics; RNA; RNA sequencing; Scientific equipment and supplies industry; Scientific imaging; Signal transduction; Small cell lung carcinoma; Survival; Tumorigenesis
• ISSN: 1745-6150; 1745-6150
• DOI: 10.1186/s13062-024-00452-7

Loss of ARID1A, a subunit of the SWI/SNF chromatin remodeling complex, contributes to malignant progression in multiple cancers including non-small cell lung cancer (NSCLC). In the search for key genes mediating the aggressive phenotype caused by ARID1A loss, we analyzed 3 Gene Expression Omnibus (GEO) datasets that contain RNA sequencing data from ARID1A-depleted cancer cells. PLAU was identified as a common gene that was induced in different cancer cells upon ARID1A depletion. Overexpression of PLAU positively modulated NSCLC cell growth, colony formation, cisplatin resistance, and survival under serum deprivation. Moreover, enforced expression of PLAU enhanced tumorigenesis of NSCLC cells in nude mice. Mechanistically, PLAU interacted with TM4SF1 to promote the activation of Akt signaling. TM4SF1-overexpressing NSCLC cells resembled those with PLAU overepxression. Knockdown of TM4SF1 inhibited the growth and survival and increased cisplatin sensitivity in NSCLC cells. The interaction between PLAU and TM4SF1 led to the activation of Akt signaling that endowed ARID1A-depleted NSCLC cells with aggressive properties. In addition, treatment with anti-TM4SF1 neutralizing antibody reduced the growth, cisplatin resistance, and tumorigenesis of ARID1A-depleted NSCLC cells. Taken together, PLAU serves as a target gene of ARID1A and promotes NSCLC growth, survival, and cisplatin resistance by stabilizing TM4SF1. Targeting TM4SF1 may be a promising therapeutic strategy for ARID1A-mutated NSCLC.