Abstract 1999: DCAF7 acts as a scaffold to recruit USP10 for G3BP1 deubiquitylation and facilitates chemoresistance and metastasis in nasopharyngeal carcinoma

Abstract Though docetaxel plus cisplatin and 5-fluorouracil (TPF) induction chemotherapy becomes the standard care for locoregionally advanced nasopharyngeal carcinoma (NPC), some patients could not benefit from this therapy. The underlying mechanisms remain unclear. We found that DCAF7 was highly expressed in TPF resistant NPC patients, and promoted the cisplatin resistance and metastasis of NPC cells. Mechanistically, DCAF7 facilitates the interaction between USP10 and G3BP1, resulting in the removal of K48-linked ubiquitylation of G3BP1 at Lys76 mediated by USP10, thus preventing the degradation of G3BP1 through ubiquitin-proteasome pathway, and facilitates the stress granule (SG)-like structures formation. Moreover, knockdown of G3BP1 successfully reversed the SG-like structures formation and oncogenic effects exerted by DCAF7. Importantly, NPC patients with elevated DCAF7 expression exhibited high risks of metastasis, and is associated with a poor prognosis. This study identifies DCAF7 as a pivotal cisplatin resistance gene, and sheds light on the underlying mechanism of TPF resistance in NPC patients. The DCAF7-USP10-G3BP1 axis provides potential therapeutic targets and biomarker for NPC treatment. Citation Format: Qing-Jie Li, Xue-Liang Fang, Ying-Qin Li, Jia-Yi Lin, Cheng-Long Huang, Shi-Wei He, Sheng-Yan Huang, Jun-Yan Li, Sha Gong, Kai-Lin Chen, Na Liu, Jun Ma, Yin Zhao, Ling-Long Tang. DCAF7 acts as a scaffold to recruit USP10 for G3BP1 deubiquitylation and facilitates chemoresistance and metastasis in nasopharyngeal carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1999.