ABC Transporters in Cancer Stem Cells: Beyond Chemoresistance.
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The efficacy of chemotherapy is one of the main challenges in cancer treatment and one of the major obstacles to overcome in achieving lasting remission and a definitive cure in patients with cancer is the emergence of cancer resistance. Indeed, drug resistance is ultimately accountable for poor treatment outcomes and tumour relapse. There are various molecular mechanisms involved in multidrug resistance, such as the change in the activity of membrane transporters primarily belonging to the ATP binding cassette (ABC) transporter family. In addition, it has been proposed that this common feature could be attributed to a subpopulation of slow-cycling cancer stem cells (CSCs), endowed with enhanced tumorigenic potential and multidrug resistance. CSCs are characterized by the overexpression of specific surface markers that vary in different cancer cell types. Overexpression of ABC transporters has been reported in several cancers and more predominantly in CSCs. While the major focus on the role played by ABC transporters in cancer is polarized by their involvement in chemoresistance, emerging evidence supports a more active role of these proteins, in which they release specific bioactive molecules in the extracellular milieu. This review will outline our current understanding of the role played by ABC transporters in CSCs, how their expression is regulated and how they support the malignant metabolic phenotype. To summarize, we suggest that the increased expression of ABC transporters in CSCs may have precise functional roles and provide the opportunity to target, particularly these cells, by using specific ABC transporter inhibitors.
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Deshmukh, Abhijeet; Arfuso, Frank; Newsholme, Philip; Dharmarajan, Arunasalam (2018)© 2018 by the authors. Licensee MDPI, Basel, Switzerland. Tumours contain a small number of treatment-resistant cancer stem cells (CSCs), and it is through these that tumour regrowth originates at secondary sites, thus ...
Breast cancer stem-like cells are inhibited by diosgenin, a steroidal saponin, by the attenuation of the Wnt ß-catenin signaling via the Wnt antagonist secreted frizzled related protein-4Bhuvanalakshmi, G.; Basappa; Rangappa, K.; Dharmarajan, Arunasalam; Sethi, Gautam; Kumar, Alan Prem; Warrier, Sudha (2017)Background: Identification of breast cancer stem cells as the chemo-resistant and tumor-initiating population represents an important milestone in approaching anticancer therapies. Targeting this minor subpopulation of ...
Deshmukh, A.; Deshpande, K.; Arfuso, F.; Newsholme, P.; Dharmarajan, Arunasalam (2016)© 2016 The Author(s). Cancer Stem cells (CSCs) are a unipotent cell population present within the tumour cell mass. CSCs are known to be highly chemo-resistant, and in recent years, they have gained intense interest as ...