promotes expression of and in enhancing breast cancer stemness and metastasis.

Cancer metastasis is largely incurable and accounts for 90% of breast cancer deaths, especially for the aggressive basal-like or triple negative breast cancer (TNBC). Combining patient database analyses and functional studies, we examined the association of integrin family members with clinical outcomes as well as their connection with previously identified microRNA regulators of metastasis, such as miR-206 that inhibits stemness and metastasis of TNBC. Here we report that the integrin receptor CD49b-encoding , a direct target of miR-206, promotes breast cancer stemness and metastasis. knockdown suppressed self-renewal related mammosphere formation and pluripotency marker expression, inhibited cell cycling, compromised migration and invasion, and therefore decreased lung metastasis of breast cancer. overexpression reversed miR-206-caused cell cycle arrest in G1. RNA sequencing analyses revealed that knockdown inhibits genes related to cell cycle regulation and lipid metabolism, including and as representative targets, respectively. Knockdown of or inhibits mammosphere formation of breast cancer cells. Overexpression of rescues the phenotype of knockdown-induced cell cycle arrest. -encoded ATP citrate lyase is essential to maintain cellular acetyl-CoA levels. knockdown further mimics knockdown in abolishing lung colonization of breast cancer cells. We identified that the low levels of as well as high expression levels of , and are associated with an unfavorable relapse-free survival of the patients with estrogen receptor-negative or high grade breast cancer, especially basal-like or TNBC, possibly serving as potential biomarkers of cancer stemness and therapeutic targets of breast cancer metastasis.