File Download
  Links for fulltext
     (May Require Subscription)
Supplementary

Article: The Stress-Inducible BCL2A1 Is Required for Ovarian Cancer Metastatic Progression in the Peritoneal Microenvironment

TitleThe Stress-Inducible BCL2A1 Is Required for Ovarian Cancer Metastatic Progression in the Peritoneal Microenvironment
Authors
Keywordsovarian cancer
peritoneal metastases
BCL2A1
hypoxia
intrinsic cell apoptosis
Issue Date2021
PublisherMDPI AG. The Journal's web site is located at http://www.mdpi.com/journal/cancers/
Citation
Cancers, 2021, v. 13 n. 18, p. article no. 4577 How to Cite?
AbstractEmerging evidence indicates that hypoxia plays a critical role in governing the transcoelomic metastasis of ovarian cancer. Hence, targeting hypoxia may be a promising approach to prevent the metastasis of ovarian cancer. Here, we report that BCL2A1, a BCL2 family member, acts as a hypoxia-inducible gene for promoting tumor progression in ovarian cancer peritoneal metastases. We demonstrated that BCL2A1 was induced not only by hypoxia but also other physiological stresses through NF-κB signaling and then was gradually reduced by the ubiquitin-proteasome pathway in ascites-derived ovarian cancer cells. The upregulated BCL2A1 was frequently found in advanced metastatic ovarian cancer cells, suggesting its clinical relevance in ovarian cancer metastatic progression. Functionally, BCL2A1 enhanced the foci formation ability of ovarian cancer cells in a stress-conditioned medium, colony formation in an ex vivo omental tumor model, and tumor dissemination in vivo. Under stress conditions, BCL2A1 accumulated and colocalized with mitochondria to suppress intrinsic cell apoptosis by interacting with the BH3-only subfamily BCL2 members HRK/BAD/BID in ovarian cancer cells. These findings indicate that BCL2A1 is an early response factor that maintains the survival of ovarian cancer cells in the harsh tumor microenvironment.
Persistent Identifierhttp://hdl.handle.net/10722/304050
ISSN
2023 Impact Factor: 4.5
2023 SCImago Journal Rankings: 1.391
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorLIANG, R-
dc.contributor.authorYung, MMH-
dc.contributor.authorHe, F-
dc.contributor.authorJIAO, P-
dc.contributor.authorChan, KKL-
dc.contributor.authorNgan, HYS-
dc.contributor.authorChan, DW-
dc.date.accessioned2021-09-23T08:54:33Z-
dc.date.available2021-09-23T08:54:33Z-
dc.date.issued2021-
dc.identifier.citationCancers, 2021, v. 13 n. 18, p. article no. 4577-
dc.identifier.issn2072-6694-
dc.identifier.urihttp://hdl.handle.net/10722/304050-
dc.description.abstractEmerging evidence indicates that hypoxia plays a critical role in governing the transcoelomic metastasis of ovarian cancer. Hence, targeting hypoxia may be a promising approach to prevent the metastasis of ovarian cancer. Here, we report that BCL2A1, a BCL2 family member, acts as a hypoxia-inducible gene for promoting tumor progression in ovarian cancer peritoneal metastases. We demonstrated that BCL2A1 was induced not only by hypoxia but also other physiological stresses through NF-κB signaling and then was gradually reduced by the ubiquitin-proteasome pathway in ascites-derived ovarian cancer cells. The upregulated BCL2A1 was frequently found in advanced metastatic ovarian cancer cells, suggesting its clinical relevance in ovarian cancer metastatic progression. Functionally, BCL2A1 enhanced the foci formation ability of ovarian cancer cells in a stress-conditioned medium, colony formation in an ex vivo omental tumor model, and tumor dissemination in vivo. Under stress conditions, BCL2A1 accumulated and colocalized with mitochondria to suppress intrinsic cell apoptosis by interacting with the BH3-only subfamily BCL2 members HRK/BAD/BID in ovarian cancer cells. These findings indicate that BCL2A1 is an early response factor that maintains the survival of ovarian cancer cells in the harsh tumor microenvironment.-
dc.languageeng-
dc.publisherMDPI AG. The Journal's web site is located at http://www.mdpi.com/journal/cancers/-
dc.relation.ispartofCancers-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectovarian cancer-
dc.subjectperitoneal metastases-
dc.subjectBCL2A1-
dc.subjecthypoxia-
dc.subjectintrinsic cell apoptosis-
dc.titleThe Stress-Inducible BCL2A1 Is Required for Ovarian Cancer Metastatic Progression in the Peritoneal Microenvironment-
dc.typeArticle-
dc.identifier.emailYung, MMH: mhyung@hku.hk-
dc.identifier.emailHe, F: hff1314@HKUCC-COM.hku.hk-
dc.identifier.emailChan, KKL: kklchan@hkucc.hku.hk-
dc.identifier.emailNgan, HYS: hysngan@hkucc.hku.hk-
dc.identifier.emailChan, DW: dwchan@HKUCC-COM.hku.hk-
dc.identifier.authorityChan, KKL=rp00499-
dc.identifier.authorityNgan, HYS=rp00346-
dc.identifier.authorityChan, DW=rp00543-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.3390/cancers13184577-
dc.identifier.pmid34572804-
dc.identifier.scopuseid_2-s2.0-85114950231-
dc.identifier.hkuros325611-
dc.identifier.volume13-
dc.identifier.issue18-
dc.identifier.spagearticle no. 4577-
dc.identifier.epagearticle no. 4577-
dc.identifier.isiWOS:000699366600001-
dc.publisher.placeSwitzerland-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats