Alpha-Tubulin Acetylation: A Key Player in Breast Cancer Metastasis

Introduction

Breast cancer (BC) is the most frequently diagnosed cancer and is associated with the most cancer-related deaths in women globally¹. BC occurs in women of all ages after puberty¹. In 2022, 2.3 million women were diagnosed with BC causing approximately 670,000 deaths worldwide¹. Despite the progress made in the early detection and treatment of BC, metastasis, however, significantly complicates treatment and remains the major cause of cancer-related deaths^2,3. Metastasis refers to the process in which cancer cells spread from the primary tumor site to establish in different anatomical sites². These spreading cells are hard to treat, grow rapidly, and can lead to organ failure at the metastasized site⁴. Thus, understanding the detailed molecular mechanisms that drive BC metastasis will be crucial in developing more effective therapeutic interventions.

Acetylation of α-tubulin is one such mechanism that has been linked with BC progression and metastasis^3,5–7. It is a posttranslational modification (PTM) that typically occurs on lysine 40 of α-tubulin—a critical protein that dimerizes with β-tubulin.  These heterodimers are the building blocks that polymerize to form microtubules (MTs) within cells^5,8.  PTMs such as acetylation and detyrosination have been associated with cell transformation in cancer⁹. For example, the acetylation of α-tubulin has been shown to enhance cell attachment, migration, and reattachment providing a selective advantage for metastatic potential⁷. These modifications often correlate with poor cancer outcome and enhanced metastatic ability, providing a rationale for targeting them as potential therapeutics^7,9. This newsletter will explore the role of α-tubulin acetylation in BC metastasis, its biological significance, and its therapeutic potential.

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Also Included in This Newsletter:

- Tubulin and Microtubule tools

- Related Publications