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NAT10 inhibition promotes ac4C-dependent ferroptosis to counteract sorafenib resistance in nasopharyngeal carcinoma.
Xue, Ziyi; Xie, Haijing; Shan, Ying; Zhang, Lin; Cheng, Lin; Chen, Wenyue; Zhu, Rui; Zhang, Kaiwen; Ni, Haosheng; Zhang, Zhenxin; You, Yiwen; You, Bo.
Afiliação
  • Xue Z; Nantong University, Nantong, Jiangsu Province, China.
  • Xie H; Institute of Otolaryngology Head and Neck Surgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province, China.
  • Shan Y; Institute of Otolaryngology Head and Neck Surgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province, China.
  • Zhang L; Department of Otolaryngology Head and Neck Surgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province, China.
  • Cheng L; Institute of Otolaryngology Head and Neck Surgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province, China.
  • Chen W; Department of Otolaryngology Head and Neck Surgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province, China.
  • Zhu R; Haimen People's Hospital, Nantong, Jiangsu Province, China.
  • Zhang K; Nantong University, Nantong, Jiangsu Province, China.
  • Ni H; Institute of Otolaryngology Head and Neck Surgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province, China.
  • Zhang Z; Nantong University, Nantong, Jiangsu Province, China.
  • You Y; Institute of Otolaryngology Head and Neck Surgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province, China.
  • You B; Nantong University, Nantong, Jiangsu Province, China.
Cancer Sci ; 115(10): 3256-3272, 2024 Oct.
Article em En | MEDLINE | ID: mdl-39038928
ABSTRACT
Sorafenib, an anticancer drug, has been shown to induce ferroptosis in cancer cells. However, resistance to sorafenib greatly limits its therapeutic efficacy, and the exact mechanism of resistance is not fully understood. This study investigated the role of N-Acetyltransferase 10 (NAT10) in influencing the anticancer activity of sorafenib in nasopharyngeal carcinoma (NPC) and its molecular mechanism. NAT10 expression was significantly upregulated in NPC. Mechanistically, NAT10 promotes proteins of solute carrier family 7 member 11 (SLC7A11) expression through ac4C acetylation, inhibiting sorafenib-induced ferroptosis in NPC cells. The combined application of sorafenib and the NAT10 inhibitor remodelin significantly inhibits SLC7A11 expression and promotes ferroptosis in NPC cells. In vivo knockout of NAT10 inhibited the growth of sorafenib-resistant NPC. Our findings suggest that NAT10 inhibition might be a promising therapeutic approach to enhance the anticancer activity of sorafenib.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Nasofaríngeas / Resistencia a Medicamentos Antineoplásicos / Sistema y/ de Transporte de Aminoácidos / Sorafenibe / Carcinoma Nasofaríngeo / Ferroptose Limite: Animals / Female / Humans / Male Idioma: En Revista: Cancer Sci Ano de publicação: 2024 Tipo de documento: Article País de afiliação: China

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Nasofaríngeas / Resistencia a Medicamentos Antineoplásicos / Sistema y/ de Transporte de Aminoácidos / Sorafenibe / Carcinoma Nasofaríngeo / Ferroptose Limite: Animals / Female / Humans / Male Idioma: En Revista: Cancer Sci Ano de publicação: 2024 Tipo de documento: Article País de afiliação: China