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.
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
7888cf96-2102-4b8c-b719-5dd71f4c359d
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
8 April 2020
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
7888cf96-2102-4b8c-b719-5dd71f4c359d
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 (4), [224].
(doi:10.1038/s41419-020-2415-2).
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.
Text
ASPP1 in CRC-min
- Accepted Manuscript
More information
Accepted/In Press date: 18 March 2020
e-pub ahead of print date: 8 April 2020
Published date: 8 April 2020
Additional Information:
Funding Information:
This project was supported by the National Natural Science Foundation of China [81772827], an Academy of Medical Sciences/the Wellcome Trust Springboard Award [SBF002\1038] and Medical Research Council [MR/ S025480/1]. A.E. was supported by the Wessex Medical Trust. C.H. was supported by Gerald Kerkut Charitable Trust and University of Southampton Central VC Scholarship Scheme. Yilu Zhou was supported by an Institute for Life Sciences PhD Studentship. Yanmei Zou was supported by the Natural Science Foundation of Hubei Province [2018CFB611]. X.L. was supported by the Ludwig Institute for Cancer Research Ltd and the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC). We thank Senji Shirasawa for providing HKe3 cells and Julian Downward for providing HKe3 ER:HRAS V12 and MCF10A ER:HRAS V12 cells.
Publisher Copyright:
© 2020, The Author(s).
Identifiers
Local EPrints ID: 438882
URI: http://eprints.soton.ac.uk/id/eprint/438882
ISSN: 2041-4889
PURE UUID: b925f3b5-91b5-4d63-9efb-f291b302a4ee
Catalogue record
Date deposited: 26 Mar 2020 17:30
Last modified: 17 Mar 2024 03:48
Export record
Altmetrics
Contributors
Author:
Dian Liu
Author:
Charlotte Hill
Author:
Yanmei Zou
Author:
Hong Qiu
Author:
Xianglin Yuan
Author:
Xin Lu
Author:
Hua Xiong
Download statistics
Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.
View more statistics
