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

doi:10.1038/ncomms11798

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^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

38 Scopus citations

Abstract

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.

Original language	English
Article number	11798
Journal	Nature Communications
Volume	7
DOIs	https://doi.org/10.1038/ncomms11798
State	Published - 16 Jun 2016

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@article{3098d92a10d147c29e8914edf5d909eb,

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

abstract = "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.",

author = "Liu, {Chen Chi} and Lin, {Shih Pei} and Hsu, {Han Shui} and Yang, {Shung Haur} and Lin, {Chiu Hua} and Yang, {Muh Hwa} and Hung, {Mien Chie} and Hung, {Shih Chieh}",

note = "Funding Information: This study was supported by grants from the Ministry of Science and Technology (MOST 103-2321-B-010-024; MOST 103-2321-B-010-018) and the Academia Sinica Translational Medicine Program (5202401023-2325)",

year = "2016",

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day = "16",

doi = "10.1038/ncomms11798",

language = "English",

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journal = "Nature Communications",

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T1 - Suspension survival mediated by PP2A-STAT3-Col XVII determines tumour initiation and metastasis in cancer stem cells

AU - Liu, Chen Chi

AU - Lin, Shih Pei

AU - Hsu, Han Shui

AU - Yang, Shung Haur

AU - Lin, Chiu Hua

AU - Yang, Muh Hwa

AU - Hung, Mien Chie

AU - Hung, Shih Chieh

N1 - Funding Information: This study was supported by grants from the Ministry of Science and Technology (MOST 103-2321-B-010-024; MOST 103-2321-B-010-018) and the Academia Sinica Translational Medicine Program (5202401023-2325)

PY - 2016/6/16

Y1 - 2016/6/16

N2 - 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.

AB - 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.

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SN - 2041-1723

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JO - Nature Communications

JF - Nature Communications

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

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