Cancer cells exploit the epithelial-to-mesenchymal transition (EMT) program toward metastasis. Cytoskeletal regulators are dually required in mesenchymal cells by promoting EMT-induced migration and sustaining the EMT program itself. In search for novel regulators of metastasis, we conducted an shRNA screen targeting a class of microtubule regulators, the plus-end tracking proteins (+TIPs). We show that the +TIP ACF7 is required for both the maintenance of EMT and to promote migration. We identified HectD1 as a potent E3 ubiquitin ligase mediating ACF7 degradation. Depletion of HectD1 robustly increases ACF7 protein levels and this is sufficient to enhance migration and EMT in cells, as well as facilitate metastasis in vivo. Ours results report the HectD1/ACF7 axis as a novel regulator of metastasis of breast cancer cells. SOURCE: Stephanie Duhamel (stephanie.duhamel@ircm.qc.ca) -  IRCM

Pluto Bioinformatics

GSE100092: The E3 ubiquitin ligase HectD1 suppresses EMT and metastasis by targeting the +TIP protein ACF7 for degradation