What role do bitter taste receptors play in cancer?

A person’s perception of bitter taste is initiated by the TAS2Rs, a family of G protein-coupled receptors that were originally identified in type II taste receptor cells (taste cells) found in the mouth. However, TAS2Rs are now known to be widely expressed throughout the body in non-taste tissues, suggesting that they play an additional role in addition to taste perception. Putative functions of TAS2Rs in cancer have been reported since the 1970s, but to date no causal relationship has been established.

To determine the current state of knowledge about the role of TAS2Rs in cancer, researchers from the University of Vienna, the Leibniz Institute for Food Systems Biology at the Technical University of Munich and the Medical University of Vienna analyzed extensive data collected using PubMed and Google Scholar. . The systemic review was published in Cancer.

Technology networks recently had the pleasure of speaking with two of the study authors, Dr. Agnes Mistlberger-Reiner and Sofie Zehentner to learn more about their findings.

Laura Lansdowne (LL): Could you tell us more about TAS2Rs and their expression in non-taste tissues?

Agnès Mistlberger-Reiner (AM-R): Since the discovery of bitter taste receptors more than two decades ago, TAS2Rs have also been found in the gastrointestinal tract and beyond in many extra-oral tissues, including the respiratory tract, heart, thyroid, kidneys, pancreas, skin, testicles, uterus, breasts and brain. as well as in blood and immune cells.

Activation of these ectopically expressed TAS2Rs by bitter-tasting compounds has been associated with tissue-specific functional responses. As functional responses depend on the type of cell that has been activated, they are quite diverse. So far, only certain non-taste functionalities have been studied such as stimulated proton secretion of gastric parietal cells, satiety hormone secretion, involvement of TAS2R in anti-inflammatory processes as well as intracellular mobilization of the calcium leading to the release of nitric oxide and antimicrobial peptides in the respiratory cells of the airways. In addition, in recent years, various effects on anticancer mechanisms have been reported, which we have examined in detail in our systematic review on the role of bitter taste receptors in cancer.

LL: Could you outline the evidence suggesting that TAS2Rs play a role in carcinogenesis?

Sofie Zehentner (SZ): At first, we found evidence for both downregulation and upregulation in the literature, although downregulation of various TAS2Rs is more prevalent. There are still limitations and the underlying mechanism, as well as the effect on cancer progression, are poorly explored. Nevertheless, the detected differential expression levels of the TAS2Rs underline their potential functional role in carcinogenesis. As highlighted in our systematic review, recent studies have shown that activation of bitter taste receptors in cancer cells is primarily associated with anticancer effects and that downregulation of certain TAS2Rs is associated with poor prognosis, while that overexpression neutralized the cancer-promoting effects. These results support our hypothesis that TAS2Rs play a functional role in carcinogenesis and that their activation counteracts the most typical abilities of cancer cells during cancer development and progression, known as hallmarks of cancer, as preventing growth suppression, deregulating cellular energetics and apoptosis as well as promoting invasive and metastatic abilities. Therefore, downregulation of TAS2Rs might facilitate the avoidance of anticancer effects mediated by TAS2R activation.

Representation of the model of the bitter taste receptor TAS2R10. Credit: Dr Jürgen Behr/ Leibniz-LSB to the Technical University of Munich.

LL: What do we know about the relationship between the taste perception of bitter compounds, diet and the incidence of certain cancers?

AM-R: Based on current scientific data, the hypothesis that bitter taste sensitivity affects the consumption of bitter-tasting foods and, therefore, has an impact on the risk of developing cancer, cannot be confirmed. To better understand the role of bitter taste sensitivity in cancer risk, more detailed sensory assessments of a variety of compounds along with quantitative analysis of dietary intake would be helpful in identifying as yet unknown relationships. Furthermore, it needs to be clarified how the sensitivity to bitterness that we perceive in the mouth can be translated into sensitivity in other organs. The extent of absorption and bioavailability of various bitter substances must be investigated, which will be difficult due to the variety of different bitter substances activating different bitter taste receptors to different degrees. In addition, there is a lack of quantitative data on many bitter substances in foods and the concentrations in itself vary widely depending on several factors such as variety, growing region, climate, food processing and preparation. Thus, the question of whether specific TAS2Rs and/or their variants, inducing distinct bitter sensitivity, play a functional role in carcinogenesis in a population group characterized by dietary habits and/or socio-demographic factors such as age or gender remains to be determined. be elucidated.

LL: Could you discuss the usefulness of TAS2Rs as targets for the development of new cancer therapies?

SZ: At this time, we can only offer hypotheses as scientific data is limited and further research is still needed in all areas. We suggest that specific bitter substances could be transported specifically to the tumor site in order to activate the TAS2Rs of cancer cells and thus inhibit tumor growth. Additionally, if chemotherapeutic agents are proven to activate different TAS2Rs leading to other anti-cancer effects via mechanisms still unknown, chemotherapeutic agents could be delivered more specifically by adapting to bitter taste receptors present in cancerous tissues. With our systematic review on the role of bitter receptors in cancer, we want to demonstrate the potential of bitter receptors as a target for cancer therapies and thus initiate research in this area. It is possible that bitter receptors may be involved in the treatment of different types of cancer in the future. However, much research is still needed.

LL: In the press release, Professor Veronika Somoza noted that “there is much to suggest that bitter taste receptors are involved in the cellular mechanisms of cancer, making them attractive targets for the development of new therapeutics. . Therefore, we intend to further explore the functions of bitter taste receptors in the future”. Could you elaborate on any other work you have done in this area or plan to do ?

AM-R: Within the framework of the project “Improvement of taste perception by homoeriodictyol (HED) in cancer patients after chemotherapy” funded by the Vienna Science and Technology Fund, we are studying the mechanisms of action of chemotherapeutic agents and HED, a bitter masking compound, on taste receptors, taste perception and taste cell function. We aim to elucidate a new approach to treat taste dysfunctions in cancer patients to improve taste perception, food intake and quality of life.

Reference: Zehentner S, Reiner AT, Grimm Ch, Somoza V. The role of bitter taste receptors in cancer: a systematic review. Cancer. 2021;13(23):5891. doi: 10.3390/cancers13235891.

Agnes Mistlberger-Reiner and Sofie Zehentner spoke with Technology Networks editor Laura Elizabeth Lansdowne.

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