Abstract
Simple SummaryBitter taste receptors (TAS2Rs) are functionally expressed in various extra-oral cells eliciting non-gustatory functions. In the context of cancer, their functionality is less clear, despite growing interest in recent years. This is the first systematic review that summarizes the current knowledge on the role of TAS2Rs in cancer from different perspectives, from cellular mechanisms of cancer to sensory perception. Although the association between TAS2R-mediated bitterness sensitivity, dietary intake and cancer risk is so far inconclusive, the majority of studies provide evidence for the downregulated gene expression of some functional TAS2Rs in cancerous compared to non-cancerous cell lines and tissue samples. Additionally, the agonist-related activation and overexpression of TAS2Rs per se induced various anti-cancer effects, leading to the hypothesis that TAS2Rs impact carcinogenesis and could serve as a target in cancer therapy by interfering with typical capabilities of cancerous cells, known as the hallmarks of cancer.Background: Since it is known that bitter taste receptors (TAS2Rs) are expressed and functionally active in various extra-oral cells, their genetic variability and functional response initiated by their activation have become of broader interest, including in the context of cancer. Methods: A systematic research was performed in PubMed and Google Scholar to identify relevant publications concerning the role of TAS2Rs in cancer. Results: While the findings on variations of TAS2R genotypes and phenotypes and their association to the risk of developing cancer are still inconclusive, gene expression analyses revealed that TAS2Rs are expressed and some of them are predominately downregulated in cancerous compared to non-cancerous cell lines and tissue samples. Additionally, receptor-specific, agonist-mediated activation induced various anti-cancer effects, such as decreased cell proliferation, migration, and invasion, as well as increased apoptosis. Furthermore, the overexpression of TAS2Rs resulted in a decreased tumour incidence in an in vivo study and TAS2R activation could even enhance the therapeutic effect of chemotherapeutics in vitro. Finally, higher expression levels of TAS2Rs in primary cancerous cells and tissues were associated with an improved prognosis in humans. Conclusion: Since current evidence demonstrates a functional role of TAS2Rs in carcinogenesis, further studies should exploit their potential as (co-)targets of chemotherapeutics.
Highlights
Cancer patients frequently experience taste alterations, such as bitter taste dysgeusia, as a side effect of chemotherapy [1,2,3], likely by chemotherapeutic drugs interfering with the pathways of cell proliferation of taste cells [4], and even by impacting the expression of taste receptors [5]
Several recent studies [36,37,38,39,40,41,42,43,44,45,46] have examined the role of bitter taste perception in cancer development, focusing on the question of whether genetic variations of TAS2Rs impact the risk for developing cancer directly as well as indirectly via different dietary intake caused by the gene-mediated variability of bitter taste sensitivity
The following hypotheses from different perspectives are discussed: (i) an increased bitterness perception leads to the avoidance of bitter-tasting foods with health-promoting phytochemicals and, as a consequence, increases cancer risk [36,38]; (ii) an elevated sensitivity of TAS2Rs to bitter-tasting compounds is protective against bittertasting carcinogenic compounds, leading to a decreased cancer risk [37,40,41]; (iii) cancer risk is influenced by genetic variants via TAS2R-related, tissue-specific functions [44]
Summary
Cancer patients frequently experience taste alterations, such as bitter taste dysgeusia, as a side effect of chemotherapy [1,2,3], likely by chemotherapeutic drugs interfering with the pathways of cell proliferation of taste cells [4], and even by impacting the expression of taste receptors [5]. As the efficacy of chemotherapeutic treatments was shown to be associated with the recurrence of regular taste perception [6], the risk for bitter taste dysgeusia was hypothesized to be linked to an increasing spread of cancer [7] This hypothesis is supported by the discovery that altered bitter taste perception even preceded chemotherapy [7,8], and was, discussed as a side effect of cancer [6]. TAS2Rs are expressed in the oral cavity; they have been found in the gastrointestinal tract [9,11] and beyond in many extra-oral tissues [11,12,13] The activation of these ectopically expressed TAS2Rs by bitter-tasting compounds has been associated with tissue-specific, functional responses. Conclusion: Since current evidence demonstrates a functional role of TAS2Rs in carcinogenesis, further studies should exploit their potential as (co-)targets of chemotherapeutics
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