GULP1 regulates the NRF2-KEAP1 signaling axis in urothelial carcinoma
Masamichi Hayashi, Elisa Guida, Yoshikuni Inokawa, Rachel Goldberg, Leonardo Oliveira Reis, Akira Ooki, Manohar Pilli, Pritam Sadhukhan, Juhyung Woo, Woonyoung Choi, Evgeny Izumchenko, Leonel Maldonado Gonzalez, Luigi Marchionni, Alex Zhavoronkov, Mariana Brait, Trinity J. Bivalacqua, Alexander S. Baras, George J. Netto, Wayne M. Koch, Anju Singh, Mohammad Obaidul Hoque
Abstract
was observed in most cisplatin nonresponder cases. Silencing of GULP1 was associated with GULP1 promoter hypermethylation in cell lines and primary tumors, and a high frequency of GULP1 promoter methylation was observed in multiple sets of primary clinical UCB samples. Together, our findings demonstrate that GULP1 is a KEAP1-binding protein that regulates KEAP1-NRF2 signaling in UCB and that promoter hypermethylation of GULP1 is a potential mechanism of GULP1 silencing.