ADAM12 promotes clear cell renal cell carcinoma progression and triggers EMT via EGFR/ERK signaling pathway

• Published in: Journal of translational medicine 2023-01, Vol.21 (1), p.56-56, Article 56
• Main Authors: Xu, Jinming, Wang, Yan, Jiang, Jiahao, Yin, Cong, Shi, Bentao
• Format: Article
• Language: English
• Subjects: ADAM protein; ADAM12; ADAM12 Protein - genetics; ADAM12 Protein - metabolism; Bioinformatics; Biotechnology industry; c-Myc protein; Carcinoma, Renal cell; Carcinoma, Renal Cell - pathology; Cell Line, Tumor; Cell migration; Cell Movement - genetics; Cell proliferation; Cell Proliferation - genetics; Cell survival; Cells; Clear cell renal cell carcinoma; Clear cell-type renal cell carcinoma; Cloning; Development and progression; E-cadherin; EGFR Pathway; EMT; Epidermal growth factor; Epidermal growth factor receptors; Epithelial-Mesenchymal Transition - genetics; ErbB Receptors - metabolism; Extracellular signal-regulated kinase; Gene expression; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; Kidney cancer; Kidney Neoplasms - pathology; Ligands; Medical prognosis; Mesenchyme; Metastases; Myc protein; N-Cadherin; Prognosis; Reagents; Risk factors; Signal transduction; Signal Transduction - genetics; Tumor necrosis factor-TNF; Tumor Progression; Tumors
• ISSN: 1479-5876; 1479-5876
• DOI: 10.1186/s12967-023-03913-1

Clear cell renal cell carcinoma (ccRCC) is a major worldwide health problem due to its high prevalence and mortality rate. A disintegrin and metalloproteinase 12 (ADAM12) is aberrantly expressed in various cancers and plays an important role in tumor progression. However, its explicit effect and molecular mechanism in ccRCC remain unclear. We investigated the dysregulation of ADAM12 in ccRCC through public databases and bioinformatics analyses. The expression of ADAM12 was further verified in ccRCC tissues by RT-qPCR and immunohistochemistry (IHC). The relationship between ADAM12 expression and clinicopathological characteristics was analyzed statistically. The effects of ADAM12 on the proliferation, migration and invasion of ccRCC cells were examined by in vitro and in vivo experiments. ADAM12 was significantly upregulated in ccRCC tissues and associated with poor prognosis in ccRCC patients. ADAM12 promoted ccRCC cell proliferation, migration and invasion in vitro and the growth of subcutaneous tumors in vivo. Knockdown of ADAM12 successfully suppressed its oncogenic function. Mechanistically, its overexpression induced epithelial-mesenchymal transition (EMT) by downregulating E-cadherin and upregulating N-cadherin and Snail. Moreover, ADAM12 participated in the epidermal growth factor receptor (EGFR) pathway and activated the downstream signal ERK1/2 by shedding the EGFR ligand, thereby upregulating target genes including c-Myc, enhancing cell survival and invasion ability, and promoting tumor progression, metastasis and the induction of EMT. High expression of ADAM12 induced EMT and promoted cell proliferation, migration, and invasion by activating the EGFR/ERK signaling pathway in ccRCC.