ArticleCell death & disease2022
SMOC2 promotes an epithelial-mesenchymal transition and a pro-metastatic phenotype in epithelial cells of renal cell carcinoma origin.
Article in Cell death & disease, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 24 citations in OpenAlex.
- SMOC2 promotes partial epithelial-mesenchymal transition and maladaptive repair in renal tubular epithelial cells.JCI insight · 2026Article
- Dissecting origin factors of lymph node metastasis in non-small cell lung cancer via multimodal omics.Nature communications · 2026Article
- Integrated DIA proteomics and transcriptomics unravel molecular mechanisms of uterine prolificacy in Yunshang Black goats during the estrous cycle.BMC genomics · 2026Article
- Matricellular protein SMOC2 safeguards tubular integrity in acute kidney injury via integrin β3-dependent inhibition of CCND1-CDK4/6 axis.Molecular biomedicine · 2026Article
- Identification of a prognostic signature based on ammonia metabolism-related genes in clear cell renal cell carcinoma: an integrated analysis of bulk and single-cell transcriptomics.Frontiers in immunology · 2026Article
- SMOC2 promotes peritoneal metastasis of gastric cancer involving Wnt/β-catenin pathway modulation and inducing angiogenesis.Clinical and experimental medicine · 2025Article
- The functional role of the extracellular matrix in inflammatory bowel disease associated gut fibrosis.Matrix biology : journal of the International Society for Matrix Biology · 2025Review
- Role of SMOC2 in adenomyosis: implications for ECM remodeling and EMT pathogenesis.BMC women's health · 2025Article
- Article
- Identification of signature genes and subtypes for heart failure diagnosis based on machine learning.Frontiers in cardiovascular medicine · 2025Article
- Multichannel 3D-Printed Bioactive Scaffold Combined with Small Interfering RNA Delivery to Promote Neurological Recovery after Spinal Cord Injury.Research (Washington, D.C.) · 2025Article
- Gastric metastasis of renal cell carcinoma: features, mechanisms, and insights from existing literature.Frontiers in cell and developmental biology · 2025Review
- nsDCC: dual-level contrastive clustering with nonuniform sampling for scRNA-seq data analysis.Briefings in bioinformatics · 2024Article
- Current development of molecular classifications of gastric cancer based on omics (Review).International journal of oncology · 2024Review
- Gene Misexpression in aJournal of the Endocrine Society · 2024Article
- Engineering cell-derived extracellular matrix for peripheral nerve regeneration.Materials today. Bio · 2024Review
- Plasma SMOC2 Predicts Prognosis in Patients with Heart Failure: A Prospective Cohort.International journal of general medicine · 2024Article
- The components of tumor microenvironment as biomarker for immunotherapy in metastatic renal cell carcinoma.Frontiers in immunology · 2023Review
- Construction of EMT related prognostic signature for kidney renal clear cell carcinoma, through integrating bulk and single-cell gene expression profiles.Frontiers in pharmacology · 2023Article
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Renal Cell Carcinoma (RCC) is the most common form of all renal cancer cases, and well-known for its highly aggressive metastatic behavior. SMOC2 is a recently described non-structural component of the extracellular matrix (ECM) that is highly expressed during tissue remodeling processes with emerging roles in cancers, yet its role in RCC remains elusive. Using gene expression profiles from patient samples, we identified SMOC2 as being significantly expressed in RCC tissue compared to normal renal tissue, which correlated with shorter RCC patient survival. Specifically, de novo protein synthesis of SMOC2 was shown to be much higher in the tubular epithelial cells of patients with biopsy-proven RCC. More importantly, we provide evidence of SMOC2 triggering kidney epithelial cells into an epithelial-to-mesenchymal transition (EMT), a phenotype known to promote metastasis. We found that SMOC2 induced mesenchymal-like morphology and activities in both RCC and non-RCC kidney epithelial cell lines. Mechanistically, treatment of RCC cell lines ACHN and 786-O with SMOC2 (recombinant and enforced expression) caused a significant increase in EMT-markers, -matrix production, -proliferation, and -migration, which were inhibited by targeting SMOC2 by siRNA. We further characterized SMOC2 activation of EMT to occur through the integrin β3, FAK and paxillin pathway. The proliferation and metastatic potential of SMOC2 overexpressing ACHN and 786-O cell lines were validated in vivo by their significantly higher tumor growth in kidneys and systemic dissemination into other organs when compared to their respective controls. In principle, understanding the impact that SMOC2 has on EMT may lead to more evidence-based treatments and biomarkers for RCC metastasis.
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