α-Tubulin acetylation elevated in metastatic and basal-like breast cancer cells promotes microtentacle formation, adhesion, and invasive migration

Amanda E. Boggs, Michele I. Vitolo, Rebecca A. Whipple, Monica S. Charpentier, Olga G. Goloubeva, Olga B. Ioffe, Kimberly C. Tuttle, Jana Slovic, Yiling Lu, Gordon B. Mills, Stuart S. Martin

    Research output: Contribution to journalArticle

    63 Scopus citations

    Abstract

    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.

    Original languageEnglish (US)
    Pages (from-to)203-215
    Number of pages13
    JournalCancer Research
    Volume75
    Issue number1
    DOIs
    StatePublished - Jan 1 2015

    ASJC Scopus subject areas

    • Oncology
    • Cancer Research

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  • Cite this

    Boggs, A. E., Vitolo, M. I., Whipple, R. A., Charpentier, M. S., Goloubeva, O. G., Ioffe, O. B., Tuttle, K. C., Slovic, J., Lu, Y., Mills, G. B., & Martin, S. S. (2015). α-Tubulin acetylation elevated in metastatic and basal-like breast cancer cells promotes microtentacle formation, adhesion, and invasive migration. Cancer Research, 75(1), 203-215. https://doi.org/10.1158/0008-5472.CAN-13-3563