Class III beta-tubulin, drug resistance and therapeutic approaches in cancers

Abstract

Class III beta-tubulin is one of the critical proteins associated with microtubule assembly, important to many cellular functions including mitochondrial respiration and intracellular trafficking. Widely regarded as a specific neuronal marker in developmental neurobiology and stem cell research, it is also highly expressed in a wide range of tumors of both neuronal and non-neuronal origin. The expression of class III beta-tubulin is tightly controlled at multiple levels with tissue-dependent mechanisms of regulation. For instance, class III beta-tubulin expression is under the control of estrogens in breast cancer cells but is influenced by exposure to hypoxia and poor-nutrient supply in ovarian cancer. In some but not all cancers, class III beta-tubulin expression is purely a prognostic biomarker, predicting poor outcome of patients regardless of chemotherapy treatment. Moreover, the expression of class III beta-tubulin does not confer an aggressive phenotype by itself. Instead, class III betatubulin functions like a cytoskeletal gateway, which enhances the incorporation of pro-survival kinases into the cytoskeleton and protects them from degradation. The associations of class III beta-tubulin with survival kinase PIM-1, RNA-binding protein HuR, microRNAs are examples highlighting the functional complexity of this protein. The utility of class III beta-tubulin as a prognostic biomarker can also greatly improve if combined with these pro-survival partners. Subsequently, pharmacogenetic approaches, designed to counteract and target these pathways and associated-factors concurrently, might lead to better therapies and prognostic tools for class III beta-tubulin expressing cancers.

The combination therapy of targeting both paclitaxel and Dendrophthoe pentandra leaves extract nanoparticles for improvement breast cancer treatment efficacy by reducing TUBB3 and MAP4 expressions

“…TUBB3, which is made up of microtubules, plays a role in cellular processes such as mitosis, proliferation, and cell motility (Person et al, 2017;Sadeghi et al, 2015;Zhenhua et al, 2015;Karki et al, 2014). The TUBB3 expression has a significant cycle-specificity in cell proliferation, of which the expression is increased in the G2-M phase (Endharti et al, 2018;Junhui et al, 2019;Permana et al, 2018;Sadeghi et al, 2015).…”

“…Tubulin βIII (TUBB3) is the most studied microtubule isotype in human cancer. TUBB3 over-expression was linked to poor clinical results in several cancers (Karki & Ferlini, 2014). Microtubule-associated protein 4 (MAP4) was a cytosolic microtubule which plays a significant role in maintaining vascular stability and tumorigenesis (Eduardo et al, 2017;Zhang et al, 2019).…”

Resistance to anti-tubulin agents: From vinca alkaloids to epothilones

“…It enhances the incorporation of pro-survival kinases into the cytoskeleton and protects them from degradation. The associations of βIII-tubulin with survival kinase PIM-1, RNA-binding protein HuR, microRNAs are examples highlighting the functional complexity of this protein [ 126 ] . Ovarian clear cell adenocarcinoma and estrogen-receptor negative breast cancer, where βIII-tubulin overexpression indicates beneficial outcome of taxane-based chemotherapy, seem to be exceptions [ 127 , 128 ] .…”

Promising Targeted Therapies Genes and Prognostic Biomarkers of Gastric Cancer

“…Более поздние данные о TUBB3 и эффективности различных ингибиторов митоза противоречивы. В частности, класс III бета-тубулина является чисто прогностическим биомаркером, ассоциированным с неблагоприятным исходом заболевания при некоторых солидных злокачественных опухолях, независимо от выбора химиотерапевтических препаратов [59].…”