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TMEM176B Regulates AKT/mTOR Signaling and Tumor Growth in Triple-Negative Breast Cancer
| Content Provider | MDPI |
|---|---|
| Author | Kang, Chifei Rostoker, Ran Ben-Shumel, Sarit Rashed, Rola Duty, James Andrew Demircioglu, Deniz Antoniou, Irini M. Isakov, Lika Shen-Orr, Zila Bravo-Cordero, Jose Javier Kase, Nathan Cuajungco, Math P. Moran, Thomas M. LeRoith, Derek Gallagher, Emily Jane |
| Copyright Year | 2021 |
| Description | TMEM176B is a member of the membrane spanning 4-domains (MS4) family of transmembrane proteins, and a putative ion channel that is expressed in immune cells and certain cancers. We aimed to understand the role of TMEM176B in cancer cell signaling, gene expression, cell proliferation, and migration in vitro, as well as tumor growth in vivo. We generated breast cancer cell lines with overexpressed and silenced TMEM176B, and a therapeutic antibody targeting TMEM176B. Proliferation and migration assays were performed in vitro, and tumor growth was evaluated in vivo. We performed gene expression and Western blot analyses to identify the most differentially regulated genes and signaling pathways in cells with TMEM176B overexpression and silencing. Silencing TMEM176B or inhibiting it with a therapeutic antibody impaired cell proliferation, while overexpression increased proliferation in vitro. Syngeneic and xenograft tumor studies revealed the attenuated growth of tumors with TMEM176B gene silencing compared with controls. We found that the AKT/mTOR signaling pathway was activated or repressed in cells overexpressing or silenced for TMEM176B, respectively. Overall, our results suggest that TMEM176B expression in breast cancer cells regulates key signaling pathways and genes that contribute to cancer cell growth and progression, and is a potential target for therapeutic antibodies. |
| Starting Page | 3430 |
| e-ISSN | 20734409 |
| DOI | 10.3390/cells10123430 |
| Journal | Cells |
| Issue Number | 12 |
| Volume Number | 10 |
| Language | English |
| Publisher | MDPI |
| Publisher Date | 2021-12-06 |
| Access Restriction | Open |
| Subject Keyword | Cells Oncology Tmem176b Calcium Channel Triple Negative Breast Cancer Akt/mtor Signaling Rna-seq Therapeutic Antibodies |
| Content Type | Text |
| Resource Type | Article |