SMOC2 promotes an epithelial-mesenchymal transition and a pro-metastatic phenotype in epithelial cells of renal cell carcinoma origin.
Calcium-Binding Proteins
/ metabolism
Carcinoma, Renal Cell
/ metabolism
Cell Line, Tumor
Cell Movement
/ genetics
Cell Proliferation
/ genetics
Epithelial Cells
/ metabolism
Epithelial-Mesenchymal Transition
/ genetics
Gene Expression Regulation, Neoplastic
Humans
Kidney Neoplasms
/ metabolism
Phenotype
Journal
Cell death & disease
ISSN: 2041-4889
Titre abrégé: Cell Death Dis
Pays: England
ID NLM: 101524092
Informations de publication
Date de publication:
22 07 2022
22 07 2022
Historique:
received:
23
11
2020
accepted:
01
07
2022
revised:
22
06
2022
entrez:
22
7
2022
pubmed:
23
7
2022
medline:
27
7
2022
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 35869056
doi: 10.1038/s41419-022-05059-2
pii: 10.1038/s41419-022-05059-2
pmc: PMC9307531
doi:
Substances chimiques
Calcium-Binding Proteins
0
SMOC2 protein, human
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
639Subventions
Organisme : Gouvernement du Canada | Canadian Institutes of Health Research (Instituts de Recherche en Santé du Canada)
ID : 428250
Informations de copyright
© 2022. The Author(s).
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