Suspension survival mediated by PP2A-STAT3-Col XVII determines tumour initiation and metastasis in cancer stem cells

Chen Chi Liu, Shih Pei Lin, Han Shui Hsu, Shung Haur Yang, Chiu Hua Lin, Muh Hwa Yang, Mien Chie Hung, Shih Chieh Hung*

*此作品的通信作者

研究成果: Article同行評審

37 引文 斯高帕斯(Scopus)

摘要

Targeting tumour-initiating cells (TICs) would lead to new therapies to cure cancer. We previously demonstrated that TICs have the capacity to survive under suspension conditions, while other cells undergo anoikis. Here we show that TICs exhibit increased phosphorylation levels of S727STAT3 because of PP2A inactivation. Collagen 17 gene expression is upregulated in a STAT3-dependent manner, which also stabilizes laminin 5 and engages cells to form hemidesmosome-like junctions in response. Blocking the PP2A-S727STAT3-collagen 17 pathway inhibits the suspension survival of TICs and their ability to form tumours in mice, while activation of the same pathway increases the suspension survival and tumour-initiation capacities of bulk cancer cells. The S727STAT3 phosphorylation levels correlate with collagen 17 expression in colon tumour samples, and correlate inversely with survival. Finally, this signalling axis enhances the ability of TIC to form tumours in mouse models of malignant lung cancer pleural effusion and spontaneous colon cancer metastasis.

原文English
文章編號11798
期刊Nature Communications
7
DOIs
出版狀態Published - 16 6月 2016

指紋

深入研究「Suspension survival mediated by PP2A-STAT3-Col XVII determines tumour initiation and metastasis in cancer stem cells」主題。共同形成了獨特的指紋。

引用此