Protocadherin alpha 3 inhibits lung squamous cell carcinoma metastasis and epithelial-mesenchymal transition

• Published in: Genes & genomics Vol. 44; no. 2; pp. 211 - 218
• Main Authors: Tao, Yu, Fei, Liu, Chang, Liu, Yongyu, Liu, Jianhui, Jia, Yanan, Liu, Yi, Ren
• Format: Journal Article
• Language: English
• Published: Singapore Springer Singapore 01.02.2022; Springer; Springer Nature B.V; 한국유전학회
• Subjects: Analysis; Animal Genetics and Genomics; Biomedical and Life Sciences; Cancer; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Squamous Cell - genetics; Cell cycle; Cell Line, Tumor; Cell migration; Cell Movement - genetics; Cell proliferation; Cholecystokinin; E-cadherin; Epithelial-Mesenchymal Transition - genetics; Fibronectin; Gene Expression Regulation, Neoplastic; Genetic aspects; Genomes; Genomics; Health aspects; Human Genetics; Humans; Infection; Life Sciences; Lung - pathology; Lung carcinoma; Lung Neoplasms - genetics; Lung Neoplasms - pathology; Mesenchyme; Metastases; Metastasis; Microbial Genetics and Genomics; N-Cadherin; Neoplasm Invasiveness - genetics; Plant Genetics and Genomics; Polymerase chain reaction; Prognosis; Protocadherin; Protocadherins - genetics; Research Article; Squamous cell carcinoma; Stem cells; Therapeutic targets; Transfection; Vimentin; α-Catenin; 생물학; Migration and invasion; Proliferation; Protocadherin; Lung squamous cell carcinoma
• ISSN: 1976-9571; 2092-9293
• DOI: 10.1007/s13258-021-01113-z

Background Lung squamous cell carcinoma (LUSC) is associated with poor clinical prognosis and lacks available targeted therapy. Given that the major threat of cancer is metastasis, delineation of the molecular mechanism underlying it would help devise therapeutic strategies. Objective To investigate the functional role of protocadherin alpha 3 (PCDHA3) in LUSC, as well as investigate the underlying molecular mechanism. Methods Data for PCDHA3 expression and clinical information in The Cancer Genome Atlas (TCGA) were extracted and analyzed in the UALCAN platform. Expression levels of PCDHA3 in LUSC cell lines were analyzed via RT-PCR and western blot. Overexpression of PCDHA3 was conducted via plasmid transfection. CCK-8 and cell cycle assays were utilized to investigate effect of PCDHA3 on cell proliferation. Transwell assay was used to detect migration and invasion. The underlying mechanism was demonstrated via western blot analysis. Results Our data indicate that PCDHA3 was low expressed in three kinds of LUSC cell lines and best in H520 cells. Furthermore, overexpression of PCDHA3 could significantly impair LUSC cells proliferation, invasion and migration. Moreover, PCHDA3 repressed the biomarkers of mesenchymal (N-cadherin, fibronectin and vimentin) and increased expression of epithelial markers (E-cadherin and α-catenin). On the other hand, PCDHA3 overexpression partially blocked epithelial-mesenchymal transition. Conclusions PCDHA3 suppressed the LUSC cells proliferation, invasion and migration via inhibiting the expression of EMT signatures, suggesting that PCDHA3 could serve as a valuable therapeutic target for LUSC therapy.