Tumor-suppressor function of Beclin 1 in breast cancer cells requires E-cadherin
Tobias Wijshake, Zhongju Zou, Beibei Chen, Lin Zhong, Guanghua Xiao, Yang Xie, John G. Doench, Lynda Bennett, Beth Levine
Abstract
Significance Beclin 1, an essential autophagy protein, is important for tumor suppression in mice, as well as in human breast and ovarian cancers. However, it is not well understood how Beclin 1 acts as a tumor suppressor. By performing a genetic screen to identify genes whose loss blocks the ability of Beclin 1 to inhibit the growth of breast cancer cells and follow-up biological analyses, we have identified a mechanism by which Beclin 1 prevents breast cancer growth. We found that Beclin 1 promotes the plasma membrane localization of E-cadherin, a breast tumor-suppressor molecule that restricts tumor growth and metastases only when present at the cell surface. These findings have important implications for understanding the cell biology of human breast cancer.