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. 2023 Apr 11;14:1126119. doi: 10.3389/fphar.2023.1126119

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Copyright © 2023 Otkur, Liu, Chen, Li, Ling, Lin, Yang, Xia, Qi and Piao.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Speculative summary on the mechanism of GPR35 and its antagonist on CRC cells. GPR35 expression promotes anchorage-independent growth of CRC cells by enhancing YAP/TAZ activation partly through Rho-GTPase/ROCK1/2 axis, where other unknown protein tyrosine kinase may also participate. Furthermore, GPR35 activity modulates YAP/TAZ activity by associating with other proteins or receptors in an agonist-independent manner. Antagonists, like CID-2745687 and ML145, perturb GPR35 to association with interacting protein, exhibiting an inhibitory effect on YAP/TAZ activity. On the other hand, Agonists, like zaprinast and pamoic acid, do not further promote GPR35-mediated YAP/TAZ activity but can compete with CID-2745687, attenuating the inhibitory effect of CID-2745687.