Grant: Operating Grant - Priority Announcement: Institute of Gender and Health

Endometrial cancer is the leading type of female genital cancer in the Western world and ranks fourth among the most common cancers in women. The balance between survival and apoptotic factors is crucial in determining tumour cell fate (growth vs cell death), especially during chemotherapy and metastasis. Survival and apoptosis are both regulated at the intracellular level and through extra-cellular hormones. However, how these factors interact to regulate chemoresistance and metastasis is unknown. The overall objective of the proposed research program is to examine the role of two putative key players in endometrial carcinoma chemoresistance and invasion/metastasis: Akt and TGF-beta3. Altogether, the current studies should establish the contribution of TGF-beta3 and downstream Akt isoforms in the process of HEC cell invasion/metastasis, using in vitro, ex vivo and in vivo strategies. Ultimately, this should allow us to propose multiple new avenues that could be envisaged for the treatment of chemoresistant and metastatic uterine cancers, the primary cause of cancer death. Moreover, these studies will form the basis for future investigations and provide important clues for the development of novel strategies for the treatment of endometrial cancers.