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

• DOI: 10.1186/s12967-023-03913-1
• Publication Date: 2023-01-30T09:04:29Z
• Authors: Jinming Xu; Yan Wang; Jiahao Jiang; Cong Yin; Bentao Shi
• Keywords: Clear cell renal cell carcinoma; 0301 basic medicine; Epithelial-Mesenchymal Transition; Research; ADAM12; EMT; R; ADAM12 Protein; Kidney Neoplasms; 3. Good health; ErbB Receptors; Gene Expression Regulation, Neoplastic; 03 medical and health sciences; Cell Movement; EGFR Pathway; Cell Line, Tumor; Tumor Progression; Medicine; Humans; Carcinoma, Renal Cell; Signal Transduction; Cell Proliferation

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