RRC ID 52593
著者 Nishida J, Miyazono K, Ehata S.
タイトル Decreased TGFBR3/betaglycan expression enhances the metastatic abilities of renal cell carcinoma cells through TGF-β-dependent and -independent mechanisms.
ジャーナル Oncogene
Abstract TGF-β regulates both the tumor-forming and migratory abilities of various types of cancer cells. However, it is unclear how the loss of TGF-β signaling components affects these abilities in clear-cell renal cell carcinoma (ccRCC). In this study, we investigated the role of TGFBR3 (TGF-β type III receptor, also known as betaglycan) in ccRCC. Database analysis revealed decreased expression of TGFBR3 in ccRCC tissues, which correlated with poor prognosis in patients. Orthotopic inoculation experiments using immunocompromised mice indicated that low TGFBR3 expression in ccRCC cells enhanced primary tumor formation and lung metastasis. In the presence of TGFBR3, TGF-β2 decreased the aldehyde dehydrogenase (ALDH)-positive ccRCC cell population, in which renal cancer-initiating cells are enriched. Loss of TGFBR3 also enhanced cell migration in cell culture and induced expression of several mesenchymal markers in a TGF-β-independent manner. Increased lamellipodium formation by FAK-PI3K signaling was observed with TGFBR3 downregulation, and this contributed to TGF-β-independent cell migration in ccRCC cells. Taken together, our findings reveal that loss of TGFBR3 endows ccRCC cells with multiple metastatic abilities through TGF-β-dependent and independent pathways.
巻・号 37(16)
ページ 2197-2212
公開日 2018-4-1
DOI 10.1038/s41388-017-0084-0
PII 10.1038/s41388-017-0084-0
PMID 29391598
PMC PMC5906456
MeSH Animals Carcinoma, Renal Cell / genetics Carcinoma, Renal Cell / pathology* Cell Movement / drug effects Cell Movement / genetics* Cells, Cultured Down-Regulation / genetics Gene Expression Regulation, Neoplastic Genes, Tumor Suppressor HEK293 Cells Humans Kidney Neoplasms / genetics Kidney Neoplasms / pathology* Male Mice Mice, Inbred BALB C Mice, Nude Neoplasm Metastasis Proteoglycans / genetics* Receptors, Transforming Growth Factor beta / genetics* Signal Transduction / drug effects Signal Transduction / genetics Transforming Growth Factor beta / metabolism Transforming Growth Factor beta / pharmacology Transforming Growth Factor beta / physiology*
IF 7.971
引用数 12
リソース情報
ヒト・動物細胞 OS-RC-2(RCB0735)