Targeting MUC1-C suppresses BCL2A1 in triple-negative breast cancer.

Signal Transduction and Targeted Therapy
Masayuki HirakiDonald Kufe

Abstract

B-cell lymphoma 2-related protein A1 (BCL2A1) is a member of the BCL-2 family of anti-apoptotic proteins that confers resistance to treatment with anti-cancer drugs; however, there are presently no agents that target BCL2A1. The MUC1-C oncoprotein is aberrantly expressed in triple-negative breast cancer (TNBC) cells, induces the epithelial-mesenchymal transition (EMT) and promotes anti-cancer drug resistance. The present study demonstrates that targeting MUC1-C genetically and pharmacologically in TNBC cells results in the downregulation of BCL2A1 expression. The results show that MUC1-C activates the BCL2A1 gene by an NF-κB p65-mediated mechanism, linking this pathway with the induction of EMT. The MCL-1 anti-apoptotic protein is also of importance for the survival of TNBC cells and is an attractive target for drug development. We found that inhibiting MCL-1 with the highly specific MS1 peptide results in the activation of the MUC1-C→NF-κB→BCL2A1 pathway. In addition, selection of TNBC cells for resistance to ABT-737, which inhibits BCL-2, BCL-xL and BCL-W but not MCL-1 or BCL2A1, is associated with the upregulation of MUC1-C and BCL2A1 expression. Targeting MUC1-C in ABT-737-resistant TNBC cells suppresses BCL2A1 and induces ...Continue Reading

References

May 15, 2007·The Journal of Biological Chemistry·Yumei LengDonald Kufe
Mar 6, 2009·Nature Reviews. Cancer·Kornelia Polyak, Robert A Weinberg
Nov 26, 2009·Nature Reviews. Cancer·Donald W Kufe
Nov 15, 2011·Cell Death and Differentiation·M Vogler
May 1, 2012·The Journal of Biological Chemistry·Rehan AhmadDonald Kufe
Mar 1, 2013·Proceedings of the National Academy of Sciences of the United States of America·Rizwan HaqDavid E Fisher
Nov 10, 2013·Nature Medicine·Wai Leong Tam, Robert A Weinberg
Jul 24, 2014·ACS Chemical Biology·Glenna Wink FoightAmy E Keating
Feb 26, 2015·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Masanori HasegawaDonald Kufe
Aug 13, 2015·PloS One·Deepak RainaDonald Kufe
Jan 30, 2016·Nature Reviews. Cancer·Alex R D DelbridgeDavid L Vaux
Feb 16, 2016·Journal of Medicinal Chemistry·Nicholas F PelzStephen W Fesik
Oct 19, 2016·Nature Reviews. Clinical Oncology·Giampaolo BianchiniLuca Gianni
Sep 24, 2016·Molecular Cancer Research : MCR·Maroof AlamDonald Kufe
Nov 29, 2016·Oncogene·M HirakiD Kufe
Feb 16, 2017·ACS Medicinal Chemistry Letters·Jeffrey W JohannesAlexander W Hird
Aug 9, 2017·Scientific Reports·Hasan RajabiDonald Kufe

❮ Previous
Next ❯

Citations

Nov 28, 2019·International Journal of Clinical Oncology·Takamichi IgarashiKen Shirabe
Jul 17, 2019·Molecular Cancer Therapeutics·Tsuyoshi HataDonald Kufe
Oct 3, 2020·Molecular Cancer Research : MCR·Jessica A SmartEdward J Hartsough
Mar 13, 2021·OncoTargets and Therapy·Qiaoping ZhengFuxiang Chen
May 1, 2021·European Journal of Pharmacology·Iwona RadziejewskaAnna Bielawska
May 26, 2021·European Journal of Medicinal Chemistry·Xue LiZhengyu Jiang
Jul 23, 2021·Hereditary Cancer in Clinical Practice·Leandro Jonata Carvalho OliveiraBenedito Mauro Rossi

❮ Previous
Next ❯

Methods Mentioned

BETA
xenografts
xenograft
reverse transcription PCR
PCR
immunoprecipitation
ChIP
Assay

Related Concepts

Related Feeds

Breast Cancer Triple-N

Breast cancer cells have receptors for estrogen, progesterone, HER2 receptors (also called ERBB2). Triple-negative breast cancers do not have any of these receptors. Here are the latest discoveries pertaining to triple-negative breast cancers.

B-Cell Lymphoma

B-cell lymphomas include lymphomas that affect B cells. This subtype of cancer accounts for over 80% of non-Hodgkin lymphomas in the US. Here is the latest research.

BCL-2 Family Proteins

BLC-2 family proteins are a group that share the same homologous BH domain. They play many different roles including pro-survival signals, mitochondria-mediated apoptosis and removal or damaged cells. They are often regulated by phosphorylation, affecting their catalytic activity. Here is the latest research on BCL-2 family proteins.