Novel role for the Golgi membrane protein TMEM165 in control of migration and invasion for breast carcinoma
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Pavitra Murali1, Blake P. Johnson2, Zhongpeng Lu1, Leslie Climer4, Danielle A. Scott6, Francois Foulquier3, Gabriela Oprea-Ilies5, Vladimir Lupashin4, Richard R. Drake6 and Karen L. Abbott1
1 University of Oklahoma Health Sciences Center, Department of Biochemistry and Molecular Biology, Oklahoma City, OK, United States
2 Ouchita Baptist University, Department of Biology, Arkadelphia, AR, United States
3 Centre National de la Recherche Scientifique, Unité Mixte de Recherche, Unité de Glycobiologie Structurale et Fonctionnelle, University of Lille, Lille, France
4 University of Arkansas for Medical Sciences, Department of Biophysics and Physiology, Little Rock, AR, United States
5 Emory University, Pathology and Laboratory Medicine, Atlanta, GA, United States
6 Department of Cell and Molecular Pharmacology, Medical University of South Carolina, Charleston, SC, United States
|Karen L. Abbott,||email:||[email protected]|
Keywords: TMEM165; migration; invasion; breast cancer; glycosylation
Received: December 05, 2019 Accepted: June 20, 2020 Published: July 14, 2020
The TMEM165 gene encodes for a multiple pass membrane protein localized in the Golgi that has been linked to congenital disorders of glycosylation. The TMEM165 protein is a putative ion transporter that regulates H+/Ca++/Mn++ homeostasis and pH in the Golgi. Previously, we identified TMEM165 as a potential biomarker for breast carcinoma in a glycoproteomic study using late stage invasive ductal carcinoma tissues with patient- matched adjacent normal tissues. The TMEM165 protein was not detected in non-malignant matched breast tissues and was detected in invasive ductal breast carcinoma tissues by mass spectrometry. Our hypothesis is that the TMEM165 protein confers a growth advantage to breast cancer. In this preliminary study we have investigated the expression of TMEM165 in earlier stage invasive ductal carcinoma and ductal carcinoma in situ cases. We created a CRISPR/Cas9 knockout of TMEM165 in the human invasive breast cancer cell line MDAMB231. Our results indicate that removal of TMEM165 in these cells results in a significant reduction of cell migration, tumor growth, and tumor vascularization in vivo. Furthermore, we find that TMEM165 expression alters the glycosylation of breast cancer cells and these changes promote the invasion and growth of breast cancer by altering the expression levels of key glycoproteins involved in regulation of the epithelial to mesenchymal transition such as E-cadherin. These studies illustrate new potential functions for this Golgi membrane protein in the control of breast cancer growth and invasion.
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