期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 24, 期 7, 页码 -出版社
MDPI
DOI: 10.3390/ijms24076447
关键词
renal cancer; mTOR signalling pathway; PDGFB; KLF6; CRISPR/Cas9
This study found that clear cell renal cell carcinoma (ccRCC) cells are able to secrete PDGFB, which can activate the mTORC1 signaling pathway and promote the development of ccRCC. The level of PDGFB secretion was positively correlated with the expression of intracellular KLF6 and PDGFB. Reintroduction of either KLF6 or PDGFB sustained mTORC1 signaling activity in KLF6-targeted ccRCC cells. Conditioned media of PDGFB-overexpressing ccRCC cells was able to re-activate mTORC1 activity in KLF6-targeted cells. Cancer cell-derived PDGFB can mediate mTORC1 signaling pathway activation in ccRCC, further solidifying the association between the KLF6-PDGFB axis and mTORC1 signaling pathway activity in ccRCC.
Clear cell renal cell carcinoma (ccRCC) is a hypervascular tumor that is characterized by bi-allelic inactivation of the VHL tumor suppressor gene and mTOR signalling pathway hyperactivation. The pro-angiogenic factor PDGFB, a transcriptional target of super enhancer-driven KLF6, can activate the mTORC1 signalling pathway in ccRCC. However, the detailed mechanisms of PDGFB-mediated mTORC1 activation in ccRCC have remained elusive. Here, we investigated whether ccRCC cells are able to secrete PDGFB into the extracellular milieu and stimulate mTORC1 signalling activity. We found that ccRCC cells secreted PDGFB extracellularly, and by utilizing KLF6- and PDGFB-engineered ccRCC cells, we showed that the level of PDGFB secretion was positively correlated with the expression of intracellular KLF6 and PDGFB. Moreover, the reintroduction of either KLF6 or PDGFB was able to sustain mTORC1 signalling activity in KLF6-targeted ccRCC cells. We further demonstrated that conditioned media of PDGFB-overexpressing ccRCC cells was able to re-activate mTORC1 activity in KLF6-targeted cells. In conclusion, cancer cell-derived PDGFB can mediate mTORC1 signalling pathway activation in ccRCC, further consolidating the link between the KLF6-PDGFB axis and the mTORC1 signalling pathway activity in ccRCC.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据