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EMP2 is a novel therapeutic target for endometrial cancer stem cells

Oncogene volume 36, pages 5793–5807 (2017)Cite this article

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Abstract

Previous studies have suggested that overexpression of the oncogenic protein epithelial membrane protein-2 (EMP2) correlates with endometrial carcinoma progression and ultimately poor survival from disease. To understand the role of EMP2 in the etiology of disease, gene analysis was performed to show transcripts that are reciprocally regulated by EMP2 levels. In particular, EMP2 expression correlates with and helps regulate the expression of several cancer stem cell associated markers including aldehyde dehydrogenase 1 (ALDH1). ALDH expression significantly promotes tumor initiation and correlates with the levels of EMP2 expression in both patient samples and tumor cell lines. As therapy against cancer stem cells in endometrial cancer is lacking, the ability of anti-EMP2 IgG1 therapy to reduce primary and secondary tumor formation using xenograft HEC1A models was determined. Anti-EMP2 IgG1 reduced the expression and activity of ALDH and correspondingly reduced both primary and secondary tumor load. Our results collectively suggest that anti-EMP2 therapy may be a novel method of reducing endometrial cancer stem cells.

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Accession codes

Accessions

Gene Expression Omnibus

Abbreviations

EMP2:

Epithelial membrane protein-2

CSC:

cancer stem cells.

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Acknowledgements

This work was generously supported by the Early Detection Research Network NCI CA-86366 (L Goodglick), CA016042 (University of California at Los Angeles Jonsson Comprehensive Cancer Center Flow Cytometry Core), Charles Drew University/UCLA NIH U54-CA-143931 (JL and MW), the NIH/National Center for Advancing Translational Sciences (NCATS) UL1TR000124, and NCI R01 CA163971 (MW).

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Authors and Affiliations

  1. Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA

    M H Kiyohara, C Dillard, J Tsui, S R Kim, L Goodglick, M Tong, C Aryasomayajula, P Najafzadeh, J Braun & M Wadehra

  2. Center to Eliminate Cancer Health Disparities, Charles Drew University, Los Angeles, CA, USA

    J Lu & M Wadehra

  3. Department of Internal Medicine David Geffen School of Medicine at UCLA Los Angeles, CA, USA

    D Sachdev, L Goodglick, J Braun & M Wadehra

  4. Department of Pathology and Laboratory Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA

    V F Torous

  5. Department of Ophthalmology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA

    W Wang & L K Gordon

  6. Medical Oncology, University of Michigan, Ann Arbor, MI, USA

    S McDermott & M S Wicha

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  1. M H Kiyohara
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Correspondence to M Wadehra.

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Competing interests

MW, LKG and JB are inventors on the University of California patents related to the anti-EMP2 IgG1 antibody presented in this work. They are also founders of Paganini Biopharma. MSW has financial holdings and is a scientific advisor for OncoMed Pharmaceuticals, Verastem, Paganini and MedImmune and receives research support from Dompe Pharmaceuticals and MedImmune. The remaining authors declare no conflict of interest.

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Kiyohara, M., Dillard, C., Tsui, J. et al. EMP2 is a novel therapeutic target for endometrial cancer stem cells. Oncogene 36, 5793–5807 (2017). https://doi.org/10.1038/onc.2017.142

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