RESUMO
The heterogeneity of tumor cell mass and the plasticity of cancer cell phenotypes in solid tumors allow for the insurgence of resistant and metastatic cells, responsible for cancer patients' clinical management's main challenges. Among several factors that are responsible for increased cancer aggression, metabolic reprogramming is recently emerging as an ultimate cancer hallmark, as it is central for cancer cell survival and self-renewal, metastasis and chemoresistance. The P2X7 receptor, whose expression is upregulated in many solid and hematological malignancies, is also emerging as a good candidate in cancer metabolic reprogramming and the regulation of stem cell proliferation and differentiation. Metabostemness refers to the metabolic reprogramming of cancer cells toward less differentiated (CSCs) cellular states, and we believe that there is a strong correlation between metabostemness and P2X7 receptor functions in oncogenic processes. Here, we summarize important aspects of P2X7 receptor functions in normal and tumor tissues as well as essential aspects of its structure, regulation, pharmacology and its clinical use. Finally, we review current knowledge implicating P2X7 receptor functions in cancer-related molecular pathways, in metabolic reprogramming and in metabostemness.
Assuntos
Carcinogênese/metabolismo , Neoplasias/metabolismo , Células-Tronco Neoplásicas/metabolismo , Oncogenes/fisiologia , Receptores Purinérgicos P2X7/metabolismo , Diferenciação Celular/fisiologia , Humanos , Células-Tronco Neoplásicas/patologiaRESUMO
Metastasis is the worst prognosis predictor in the clinical course of cancer development. Features of metastatic cancer cells include migratory ability, low degree of differentiation, self-renewal and proliferation potentials, as well as resistance to therapies. Metastatic cells do not present all of the necessary characteristics at once. Indeed, they have a unique phenotypic plasticity, allowing the acquisition of features that make them successful in all steps of metastasis. Cancer stem cells (CSC), the most undifferentiated cells in the tumor mass, display highest metastatic potential and resistance to radio- and chemotherapy. Growing tumors exhibit marked upregulation of P2X7 receptor expression and secrete ATP. Since the P2X7 receptor plays an important role in the maintenance of undifferentiated state of pluripotent cells, its importance on cell fate regulation in the tumor mass is suggested. Considering the extensive crosstalk between CSCs, epithelial-mesenchymal transition, drug resistance and metastasis, current knowledge implicating P2X7 receptor function in these phenomena and new avenues for therapeutic strategies to control metastasis are reviewed.