Metastatic cases of
breast cancer pose the primary challenge in clinical management of this disease, demanding the identification of effective therapeutic strategies that remain wanting. In this study, we report that elevated levels of α-
tubulin acetylation are a sufficient cause of metastatic potential in
breast cancer. In suspended cell culture conditions, metastatic
breast cancer cells exhibited high α-
tubulin acetylation levels that extended along microtentacle (McTN) protrusions. Mutation of the acetylation site on α-
tubulin and enzymatic modulation of this posttranslational modification exerted a significant impact on McTN frequency and the reattachment of suspended
tumor cells. Reducing α-
tubulin acetylation significantly inhibited migration but did not affect proliferation. In an analysis of more than 140 matched primary and metastatic
tumors from patients, we found that acetylation was maintained and in many cases increased in
lymph node metastases compared with primary
tumors. Proteomic analysis of an independent cohort of more than 390 patient specimens further documented the relationship between increased α-
tubulin acetylation and the aggressive behaviors of basal-like breast
cancers, with a trend toward increased risk of
disease progression and death in patients with high-intensity α-
tubulin acetylation in primary
tumors. Taken together, our results identify a tight correlation between acetylated α-
tubulin levels and aggressive metastatic behavior in
breast cancer, with potential implications for the definition of a simple prognostic
biomarker in patients with
breast cancer.