Pluto Bioinformatics

GSE124209: Autophagic turnover of NBR1 restricts metastatic colonization during mammary tumor progression

Bulk RNA sequencing

Autophagy is implicated in promoting the metastatic potential of tumor cells. Utilizing a mouse model of mammary cancer to temporally delete essential autophagy regulators, ATG12 or ATG5, in tumor cells during distinct stages of carcinoma progression, we determine a stage-specific role for autophagy in suppressing metastatic colonization. In stark contrast to the tumor-promoting role of autophagy in primary mammary tumors, autophagy restricts colonization of disseminated tumor cells (DTCs) and prevents the acquisition of basal epithelial characteristics, effects that are dependent on turnover of the autophagy-specific substrate, Neighbor to BRCA1 (NBR1). Analysis of human breast cancer samples corroborates the importance of NBR1 in overall survival and metastasis, highlighting NBR1 as a potential therapeutic target in preventing DTCs from developing into overt, clinical disease. SOURCE: Timothy MarshJayanta Debnath University of California, San Francisco