The Role of Bitter Taste Receptors in Cancer: A Systematic Review

Abstract

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.

Orphan receptors in prostate cancer

“…61 Bitter taste receptors (TAS2Rs) have been identified in nongustatory organs and have been linked to various diseases, including cancer. 62 In several tumor types, TAS2R activation exerts various anticancer effects, such as increased apoptosis and decreased cell proliferation and migration. 24,62,63 The expression levels of most TAS2Rs are diminished in prostate cancer cell lines compared to benign prostatic hyperplasia.…”

“…62 In several tumor types, TAS2R activation exerts various anticancer effects, such as increased apoptosis and decreased cell proliferation and migration. 24,62,63 The expression levels of most TAS2Rs are diminished in prostate cancer cell lines compared to benign prostatic hyperplasia. 24 Recent studies suggest that noscapine causes a TAS2R14-dependent cell death induction and decreased viability in prostate cancer cells.…”

Orphan Receptors in Prostate Cancer

“…Salty and sour compounds are linked to ion channels, while bitter, sweet and umami flavours are connected to G-protein-associated receptors 45 . Bitter taste receptors (TAS2Rs) have been identified in non-gustatory organs and have been linked to various diseases, including cancer 46 . In several tumor types, TAS2R activation exerts various anti-cancer effects, such as increased apoptosis and decreased cell proliferation and migration 46,47,48 .…”

“…Bitter taste receptors (TAS2Rs) have been identified in non-gustatory organs and have been linked to various diseases, including cancer 46 . In several tumor types, TAS2R activation exerts various anti-cancer effects, such as increased apoptosis and decreased cell proliferation and migration 46,47,48 . The expression levels of most TAS2Rs are diminished in prostate cancer cell lines compared to benign prostatic hyperplasia 47 .…”

“…In general, most TAS2Rs exert anticancer effects. A notable exception is TAS2R38, which is frequently overexpressed in cancer compared to normal tissue 46 . TAS2R38 can upregulate multidrug resistance protein ABCB1 and can induce chemoresistance in several tumor types 46 .…”