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ASPP1 deficiency promotes epithelial-mesenchymal transition, invasion and metastasis in colorectal cancer

ASPP1 deficiency promotes epithelial-mesenchymal transition, invasion and metastasis in colorectal cancer
ASPP1 deficiency promotes epithelial-mesenchymal transition, invasion and metastasis in colorectal cancer
The apoptosis-stimulating protein of p53 (ASPP) family of proteins can regulate apoptosis by interacting with the p53 family and have been identified to play an important role in cancer progression. Previously, we have demonstrated that ASPP2 downregulation can promote invasion and migration by controlling β-catenin- dependent regulation of ZEB1, however, the role of ASPP1 in colorectal cancer (CRC) remains unclear. We analyzed data from The Cancer Genome Atlas (TCGA) and coupled this to in vitro experiments in CRC cell lines as well as to experimental pulmonary metastasis in vivo. Tissue microarrays of CRC patients with information of clinical-pathological parameters were also used to investigate the expression and function of ASPP1 in CRC. Here, we report that loss of ASPP1 is capable of enhancing migration and invasion in CRC, both in vivo and in vitro. We demonstrate that depletion of ASPP1 could activate expression of Snail2 via the NF-κB pathway and in turn, induce EMT; and this process is further exacerbated in RAS-mutated CRC. ASPP1 could be a prognostic factor in CRC, and the use of NF-κB inhibitors may provide new strategies for therapy against metastasis in ASPP1-depleted CRC patients.
2041-4889
Liu, Dian
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Ertay, Ayse
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Hill, Charlotte
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Zhou, Yilu
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Li, Juanjuan
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Zou, Yanmei
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Qiu, Hong
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Yuan, Xianglin
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Ewing, Robert
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Lu, Xin
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Xiong, Hua
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Wang, Yihua
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Liu, Dian
d8f5cd4b-9fbe-4475-ba94-4c4fe6fb4127
Ertay, Ayse
fdd0c5cb-cfb2-4e25-9343-cdc462035531
Hill, Charlotte
6d1cfed3-11b1-48af-b171-b8726ab673eb
Zhou, Yilu
1878565d-39e6-467d-a027-7320bf4cdaf2
Li, Juanjuan
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Zou, Yanmei
70f6fe01-220c-43c8-8047-ece8d8dc49d9
Qiu, Hong
e7cb953a-c410-4ecc-ad66-d988ce34020b
Yuan, Xianglin
b250cf57-48ce-4f76-9f61-f058badbab92
Ewing, Robert
022c5b04-da20-4e55-8088-44d0dc9935ae
Lu, Xin
7f0f67c1-9c66-406e-8608-225d903e5c5d
Xiong, Hua
4e24c191-28ae-49a6-9e77-73a59a1340df
Wang, Yihua
f5044a95-60a7-42d2-87d6-5f1f789e3a7e

Liu, Dian, Ertay, Ayse, Hill, Charlotte, Zhou, Yilu, Li, Juanjuan, Zou, Yanmei, Qiu, Hong, Yuan, Xianglin, Ewing, Robert, Lu, Xin, Xiong, Hua and Wang, Yihua (2020) ASPP1 deficiency promotes epithelial-mesenchymal transition, invasion and metastasis in colorectal cancer. Cell Death and Disease, 11, [224]. (doi:10.1038/s41419-020-2415-2).

Record type: Article

Abstract

The apoptosis-stimulating protein of p53 (ASPP) family of proteins can regulate apoptosis by interacting with the p53 family and have been identified to play an important role in cancer progression. Previously, we have demonstrated that ASPP2 downregulation can promote invasion and migration by controlling β-catenin- dependent regulation of ZEB1, however, the role of ASPP1 in colorectal cancer (CRC) remains unclear. We analyzed data from The Cancer Genome Atlas (TCGA) and coupled this to in vitro experiments in CRC cell lines as well as to experimental pulmonary metastasis in vivo. Tissue microarrays of CRC patients with information of clinical-pathological parameters were also used to investigate the expression and function of ASPP1 in CRC. Here, we report that loss of ASPP1 is capable of enhancing migration and invasion in CRC, both in vivo and in vitro. We demonstrate that depletion of ASPP1 could activate expression of Snail2 via the NF-κB pathway and in turn, induce EMT; and this process is further exacerbated in RAS-mutated CRC. ASPP1 could be a prognostic factor in CRC, and the use of NF-κB inhibitors may provide new strategies for therapy against metastasis in ASPP1-depleted CRC patients.

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ASPP1 in CRC-min - Accepted Manuscript
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Accepted/In Press date: 18 March 2020
e-pub ahead of print date: 8 April 2020

Identifiers

Local EPrints ID: 438882
URI: http://eprints.soton.ac.uk/id/eprint/438882
ISSN: 2041-4889
PURE UUID: b925f3b5-91b5-4d63-9efb-f291b302a4ee
ORCID for Robert Ewing: ORCID iD orcid.org/0000-0001-6510-4001
ORCID for Yihua Wang: ORCID iD orcid.org/0000-0001-5561-0648

Catalogue record

Date deposited: 26 Mar 2020 17:30
Last modified: 07 Oct 2020 02:08

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