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 Mills, Stuart S. Martin

Research output: Contribution to journalArticle

56 Citations (Scopus)

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
Externally publishedYes

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Tubulin
Acetylation
Breast Neoplasms
Neoplasms
Post Translational Protein Processing
Disease Management
Proteomics
Disease Progression
Cohort Studies
Cell Culture Techniques
Biomarkers
Lymph Nodes
Neoplasm Metastasis
Mutation

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

Cite this

Boggs, A. E., Vitolo, M. I., Whipple, R. A., Charpentier, M. S., Goloubeva, O. G., Ioffe, O. 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

α-Tubulin acetylation elevated in metastatic and basal-like breast cancer cells promotes microtentacle formation, adhesion, and invasive migration. / Boggs, Amanda E.; Vitolo, Michele I.; Whipple, Rebecca A.; Charpentier, Monica S.; Goloubeva, Olga G.; Ioffe, Olga B.; Tuttle, Kimberly C.; Slovic, Jana; Lu, Yiling; Mills, Gordon; Martin, Stuart S.

In: Cancer Research, Vol. 75, No. 1, 01.01.2015, p. 203-215.

Research output: Contribution to journalArticle

Boggs, AE, Vitolo, MI, Whipple, RA, Charpentier, MS, Goloubeva, OG, Ioffe, OB, Tuttle, KC, Slovic, J, Lu, Y, Mills, G & Martin, SS 2015, 'α-Tubulin acetylation elevated in metastatic and basal-like breast cancer cells promotes microtentacle formation, adhesion, and invasive migration', Cancer Research, vol. 75, no. 1, pp. 203-215. https://doi.org/10.1158/0008-5472.CAN-13-3563
Boggs, Amanda E. ; Vitolo, Michele I. ; Whipple, Rebecca A. ; Charpentier, Monica S. ; Goloubeva, Olga G. ; Ioffe, Olga B. ; Tuttle, Kimberly C. ; Slovic, Jana ; Lu, Yiling ; Mills, Gordon ; Martin, Stuart S. / α-Tubulin acetylation elevated in metastatic and basal-like breast cancer cells promotes microtentacle formation, adhesion, and invasive migration. In: Cancer Research. 2015 ; Vol. 75, No. 1. pp. 203-215.
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