Inhibiting the SUMO Pathway Represses the Cancer Stem Cell Population in Breast and Colorectal Carcinomas

Maria V Bogachek; Jung M Park; James P De Andrade; Allison W Lorenzen; Mikhail V Kulak; Jeffrey R White; Vivian W Gu; Vincent T Wu; Ronald J Weigel

doi:10.1016/j.stemcr.2016.11.001

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Inhibiting the SUMO Pathway Represses the Cancer Stem Cell Population in Breast and Colorectal Carcinomas

Journal article

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Inhibiting the SUMO Pathway Represses the Cancer Stem Cell Population in Breast and Colorectal Carcinomas

Maria V Bogachek, Jung M Park, James P De Andrade, Allison W Lorenzen, Mikhail V Kulak, Jeffrey R White, Vivian W Gu, Vincent T Wu and Ronald J Weigel

Stem cell reports, Vol.7(6), pp.1140-1151

12/13/2016

DOI: 10.1016/j.stemcr.2016.11.001

PMCID: PMC5161532

PMID: 27916539

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Abstract

Many solid cancers have an expanded CD44+/hi/CD24−/low cancer stem cell (CSC) population, which are relatively chemoresistant and drive recurrence and metastasis. Achieving a more durable response requires the development of therapies that specifically target CSCs. Recent evidence indicated that inhibiting the SUMO pathway repressed tumor growth and invasiveness, although the mechanism has yet to be clarified. Here, we demonstrate that inhibition of the SUMO pathway repressed MMP14 and CD44 with a concomitant reduction in cell invasiveness and functional loss of CSCs in basal breast cancer. Similar effects were demonstrated with a panel of E1 and E3 SUMO inhibitors. Identical results were obtained in a colorectal cancer cell line and primary colon cancer cells. In both breast and colon cancer, SUMO-unconjugated TFAP2A mediated the effects of SUMO inhibition. These data support the development of SUMO inhibitors as an approach to specifically target the CSC population in breast and colorectal cancer. •Sumoylation regulates CD44 and MMP14 expression in basal breast and colon cancer•SUMO inhibition clears cancer stem cells, repressing invasiveness and tumor growth•Anacardic acid functions as a SUMO inhibitor to repress cancer stem cells•TFAP2A mediates anti-tumor effects of SUMO inhibition in breast and colon cancers Weigel and colleagues provide substantial evidence for developing cancer stem cell-specific therapy based on inhibiting the SUMO pathway. They show that inhibition of sumoylation enzymes by knockdown or small-molecule inhibitors repressed cancer stem cells with loss of CD44 and MMP14, and reduced invasiveness and inhibition of tumor growth. Common SUMO-sensitive mechanisms were dependent upon TFAP2A in breast and colon cancer.

TFAP2A

MMP14

sumoylation

cancer stem cell

colon cancer

breast cancer

CD44

Details

Title: Subtitle: Inhibiting the SUMO Pathway Represses the Cancer Stem Cell Population in Breast and Colorectal Carcinomas
Creators: Maria V Bogachek - Department of Surgery, University of Iowa, 200 Hawkins Drive, 1516 JCP, Iowa City, IA 52242, USA
Jung M Park - Department of Surgery, University of Iowa, 200 Hawkins Drive, 1516 JCP, Iowa City, IA 52242, USA
James P De Andrade - Department of Surgery, University of Iowa, 200 Hawkins Drive, 1516 JCP, Iowa City, IA 52242, USA
Allison W Lorenzen - Department of Surgery, University of Iowa, 200 Hawkins Drive, 1516 JCP, Iowa City, IA 52242, USA
Mikhail V Kulak - Department of Surgery, University of Iowa, 200 Hawkins Drive, 1516 JCP, Iowa City, IA 52242, USA
Jeffrey R White - Department of Surgery, University of Iowa, 200 Hawkins Drive, 1516 JCP, Iowa City, IA 52242, USA
Vivian W Gu - Department of Surgery, University of Iowa, 200 Hawkins Drive, 1516 JCP, Iowa City, IA 52242, USA
Vincent T Wu - Department of Surgery, University of Iowa, 200 Hawkins Drive, 1516 JCP, Iowa City, IA 52242, USA
Ronald J Weigel - Department of Surgery, University of Iowa, 200 Hawkins Drive, 1516 JCP, Iowa City, IA 52242, USA
Resource Type: Journal article
Publication Details: Stem cell reports, Vol.7(6), pp.1140-1151
DOI: 10.1016/j.stemcr.2016.11.001
PMID: 27916539
PMCID: PMC5161532
NLM abbreviation: Stem Cell Reports
ISSN: 2213-6711
eISSN: 2213-6711
Publisher: Elsevier Inc
Grant note: DOI: 10.13039/100000002, name: NIH, award: R01CA183702, T32CA148062, T32CA148062; name: Kristen Olewine Milke Breast Cancer Research Fund
Language: English
Date published: 12/13/2016
Academic Unit: Molecular Physiology and Biophysics; Anatomy and Cell Biology; Surgery; Biochemistry and Molecular Biology
Record Identifier: 9984025264102771

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