ADAM12 promotes clear cell renal cell carcinoma progression and triggers EMT via EGFR/ERK signaling pathway
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
DOI:
10.1186/s12967-023-03913-1
Publication Date:
2023-01-30T09:04:29Z
AUTHORS (5)
ABSTRACT
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.
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