The tumor suppressor TGFBR3 blocks lymph node metastasis in head and neck cancer

Wei Yu Fang, Yi Zih Kuo, Jang Yang Chang, Jenn Ren Hsiao, Hung Ying Kao, Sen Tien Tsai, Li Wha Wu

研究成果: Article同行評審

3 引文 斯高帕斯(Scopus)

摘要

The TGF-β type III receptor (TGFBR3) is an essential constituent of the TGF-β signaling. In this study, we observed a down-regulation of TGFBR3 in oral cancer, a subtype of head and neck cancer (HNC), and patients with low TGFBR3 had poor clinical outcomes. Ectopic expression of TGFBR3 decreased migration and invasion of oral cancer cells and lymph node metastasis of tumors, whereas depletion of TGFBR3 had the opposite effect. In SMAD4-positive OC-2 oral cancer cells, TGFBR3-mediated suppression requires both of its cytoplasmic interacting partners ARRB2 and GIPC1. We demonstrated that TGFBR3 induces the abundance of secreted angiogenin (ANG), a known pro-angiogenic factor, and ANG is essential and sufficient to mediate TGFBR3-dependent inhibition of migration and invasion of oral cancer cells. Notably, in SMAD4-deficient CAL-27 oral cancer cells, only GIPC1 is essential for TGFBR3-induced suppressive activity. Accordingly, HNC patients with low expressions of both TGFBR3 and GIPC1 had the poorest overall survival. In summary, we conclude that TGFBR3 is as a tumor suppressor via SMAD4-dependent and - independent manner in both tumor and stromal cells during oral carcinogenesis. Our study should facilitate the possibility of using TGFBR3-mediated tumor suppression for HNC treatment.

原文English
文章編號1375
期刊Cancers
12
發行號6
DOIs
出版狀態Published - 2020 六月

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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