Mitotic kinases as drivers of the epithelial-to-mesenchymal transition and as therapeutic targets against breast cancers
| Autor: | Yainyrette Rivera-Rivera, Shirley Jusino, Harold I. Saavedra, Stephanie Colón-Marrero |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Epithelial-Mesenchymal Transition BUB1 Aurora B kinase Mitosis Context (language use) Breast Neoplasms Biology General Biochemistry Genetics and Molecular Biology 03 medical and health sciences 0302 clinical medicine Breast cancer Chromosome instability medicine Animals Humans Epithelial–mesenchymal transition Cancer medicine.disease 030104 developmental biology 030220 oncology & carcinogenesis Cancer research Female Minireview Protein Kinases |
| Zdroj: | Exp Biol Med (Maywood) |
| Popis: | Biological therapies against breast cancer patients with tumors positive for the estrogen and progesterone hormone receptors and Her2 amplification have greatly improved their survival. However, to date, there are no effective biological therapies against breast cancers that lack these three receptors or triple-negative breast cancers (TNBC). TNBC correlates with poor survival, in part because they relapse following chemo- and radio-therapies. TNBC is intrinsically aggressive since they have high mitotic indexes and tend to metastasize to the central nervous system. TNBCs are more likely to display centrosome amplification, an abnormal phenotype that results in defective mitotic spindles and abnormal cytokinesis, which culminate in aneuploidy and chromosome instability (known causes of tumor initiation and chemo-resistance). Besides their known role in cell cycle control, mitotic kinases have been also studied in different types of cancer including breast, especially in the context of epithelial-to-mesenchymal transition (EMT). EMT is a cellular process characterized by the loss of cell polarity, reorganization of the cytoskeleton, and signaling reprogramming (upregulation of mesenchymal genes and downregulation of epithelial genes). Previously, we and others have shown the effects of mitotic kinases like Nek2 and Mps1 (TTK) on EMT. In this review, we focus on Aurora A, Aurora B, Bub1, and highly expressed in cancer (Hec1) as novel targets for therapeutic interventions in breast cancer and their effects on EMT. We highlight the established relationships and interactions of these and other mitotic kinases, clinical trial studies involving mitotic kinases, and the importance that represents to develop drugs against these proteins as potential targets in the primary care therapy for TNBC. |
| Databáze: | OpenAIRE |
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