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Microtubules and their role in cellular stress in cancer
Amelia L Parker1, Maria Kavallaris2, Joshua A McCarroll2
1Tumour Biology and Targeting Program, Children's Cancer Institute Australia, Lowy Cancer Research Centre, University of New South Wales , Sydney, NSW , Australia.
Abstract:
Microtubules are highly dynamic structures, which consist of α- and β-tubulin heterodimers, and are involved in cell movement, intracellular trafficking, and mitosis. In the context of cancer, the tubulin family of proteins is recognized as the target of the tubulin-binding chemotherapeutics, which suppress the dynamics of the mitotic spindle to cause mitotic arrest and cell death. Importantly, changes in microtubule stability and the expression of different tubulin isotypes as well as altered post-translational modifications have been reported for a range of cancers. These changes have been correlated with poor prognosis and chemotherapy resistance in solid and hematological cancers. However, the mechanisms underlying these observations have remained poorly understood. Emerging evidence suggests that tubulins and microtubule-associated proteins may play a role in a range of cellular stress responses, thus conferring survival advantage to cancer cells. This review will focus on the importance of the microtubule-protein network in regulating critical cellular processes in response to stress. Understanding the role of microtubules in this context may offer novel therapeutic approaches for the treatment of cancer.
Insights
Microtubules, crucial for cell functions, are implicated in cancer. Understanding their role in cellular stress responses could lead to new cancer treatments targeting the microtubule-protein network.
Area of Science:
- Cell Biology
- Cancer Biology
- Biochemistry
Background:
- Microtubules, composed of α- and β-tubulin, are vital for cell movement, trafficking, and mitosis.
- Tubulin-binding chemotherapeutics target microtubule dynamics to induce cancer cell death.
- Altered microtubule stability and tubulin expression are linked to poor prognosis and chemoresistance in various cancers.
Purpose of the Study:
- To review the role of the microtubule-protein network in cellular stress responses within cancer.
- To explore how understanding these mechanisms can inform novel cancer therapeutic strategies.
Main Methods:
- This review synthesizes current research on microtubule dynamics and function in cancer.
- It examines the link between microtubule alterations, cellular stress, and cancer cell survival.
- The focus is on the regulatory role of the microtubule-protein network in stress responses.
Main Results:
- Changes in microtubule stability, tubulin isotype expression, and post-translational modifications are observed in cancers.
- These microtubule alterations correlate with poor prognosis and chemotherapy resistance.
- Emerging evidence suggests tubulins and associated proteins contribute to cancer cell survival under stress.
Conclusions:
- The microtubule-protein network plays a critical role in regulating cellular processes during stress.
- Understanding these roles may unveil new therapeutic targets for cancer treatment.
- Further research into microtubule-mediated stress responses could enhance chemotherapy efficacy.
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