Research Highlights

Pothana Saikumar
Pothana Saikumar, Ph.D.

Triple negative breast cancer (TNBC) is the most aggressive form of breast cancer with high metastatic and poor survival rates. TNBCs, which represent 15-20% of total breast cancer cases, are responsible for almost 50% of deaths due to breast cancer and are highly resistant to many therapeutic approaches. One of the prominent markers with poor prognosis and high metastasis is high transforming growth factor-beta (TGF-beta) signaling activity in breast cancer. Paradoxically, TGF-beta is a growth inhibitor of early tumors; however, during breast cancer progression tumor suppressive actions of TGF-beta are subverted to promote tumor growth and metastasis. Based on TGF-beta's ability to promote metastasis, TGF-beta inhibitors have been considered for breast cancer treatment. However, this approach carries the risk of developing new tumors because of TGF-beta's inability to suppress early tumor formation. Therefore, the knowledge of how TGF-beta becomes a tumor promoter from a tumor suppressor is essential to develop novel therapeutics for both cancer progression and cancer prevention. In this regard, we identified a novel gene, TMEPAIthat is overexpressed in several TNBCs, which plays a critical role in subverting the tumor suppressive effects of TGF-beta. Novel drugs that target TMEPAI would not only inhibit oncogenic functions of TGF-beta but also preserve or enhance the tumor suppressive actions of TGF-beta. We consider that these drugs will have both cancer therapeutic and cancer preventive capabilities.

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