Adenozin A2B reseptörünün kolorektal karsinogenezüzerindeki etkisinin araştirilmasi

Colorectal Cancer (CRC) is one of the most prevalent cancer types, with a highly heterogeneous mutation profile, and an incidence rate ranking third and lethality ranking second worldwide. Metastasis is an important factor in CRC mortality and recurrence, having been observed in a fourth of the patients diagnosed. While the effect of purinergic signaling components has been studied in cancer progression and metastasis, with varying contributions, research on the adenosine A2B receptor (A2BR) has been overlooked in the past due to its low affinity to adenosine. The intrinsic effects of A2BR are highly context-dependent, and research on how it may affect CRC progression and metastasis is limited. In this study, we used stable A2BR overexpressing CRC cell lines as well as A2BR selective antagonists to examine the role of A2BR in CRC progression. We observed a decrease in cancer growth upon A2BR overexpression, both in vitro and in vivo. Moreover, A2BR overexpression led to a lower migratory ability and shifted the EMT marker profile of the CRC cell lines. Once we pharmacologically inhibited the A2BR activity, we observed a significant increase in cell proliferation, migration, and invasion in the CRC cell lines as well as a shift towards a more mesenchymal EMT marker profile. Furthermore, our patient survival analyses indicate a higher overall and recurrence-free survival for CRC patients with high A2BR expression. Overall, these findings indicate a tumor-suppressive role for A2BR in CRC and that pharmacological inhibition may lead to a more aggressive phenotype.