Autophagy Regulator Becn1 Acts As A Context-Dependent Tumor Suppressor Opposing Parity-Associated And Wnt1-Driven Mammary Tumorigenesis

Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA Earlier studies reported allelic deletion of the essential autophagy regulator BECN1 in breast cancers implicating BECN1 loss and defective autophagy in tumorigenesis. Recent studies questioned the tumor suppressive role of autophagy, as Atg defects, including Becn1 deletion, suppress tumorigenesis in mouse tumor models. For the first time, we report that monoallelic Becn1 loss has a context-specific tumor-promoting function in parity-associated and WNT-driven mammary tumorigenesis. Our studies demonstrate that Becn1 heterozygocity promotes immature mammary epithelial cell expansion, Receptor Activator of NFκB (RANK) signaling and mammary tumorigenesis in cooperation with the progenitor cell-transforming WNT pathway. Similar to our mouse model, low BECN1 expression and WNT pathway activation in human breast tumors correlate with triple negative breast cancers (TNBCs), RANK axis activation and poor prognosis. Our results provide novel insight in the seemingly paradoxical role of BECN1 in tumorigenesis and the basis for further studies on pathophysiology and treatment of clinically aggressive TNBCs. Citation Format: Michelle Cicchini, Rumela Chakrabarti, Sameera Kongara, Sandy Price, Ritu Nahar, Fred Lozy, Hua Zhong, Alexei Vazquez, Yibin Kang, Vassiliki Karantza. Autophagy regulator BECN1 acts as a context-dependent tumor suppressor opposing parity-associated and WNT1-driven mammary tumorigenesis. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr LB-138. doi:10.1158/1538-7445.AM2014-LB-138