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Stearoyl-CoA Desaturase 1 Potentiates Hypoxic plus Nutrient-Deprived Pancreatic Cancer Cell Ferroptosis Resistance

Hypoxia and nutrient starvation (H/NS) microenvironment, a notable characteristic of pancreatic carcinoma, plays a critical role in cell death resistance and tumor recurrence. However, its role in ferroptosis remains to be classified. Here, we found that H/NS contributed to the pancreatic cancer cel...

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Detalles Bibliográficos
Autores principales: Gao, Jie, Zhang, Zhengyang, Liu, Yanfang, Zhang, Zining, Wang, Ming, Gong, Aihua, Xia, Lin, Liao, Xiang, Wang, Dongqing, Zhu, Haitao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8032529/
https://www.ncbi.nlm.nih.gov/pubmed/33868572
http://dx.doi.org/10.1155/2021/6629804
Descripción
Sumario:Hypoxia and nutrient starvation (H/NS) microenvironment, a notable characteristic of pancreatic carcinoma, plays a critical role in cell death resistance and tumor recurrence. However, its role in ferroptosis remains to be classified. Here, we found that H/NS contributed to the pancreatic cancer cell ferroptosis resistance depending on the altered intracellular lipid compositions. Mechanistically, H/NS induced the upregulation of stearoyl-CoA desaturase 1 (SCD1), which promoted monounsaturated fatty acids (MUFAs) synthesis and protected against lipid peroxidation. Surprisingly, SCD1 showed a strong correlation with antiferroptosis gene expression. Moreover, short-hairpin RNA-based knockdown of SCD1 enhanced erastin-induced ferroptosis in vitro under H/NS. Finally, our results demonstrate the synergistic effect of erastin and A939572, a special SCD1 inhibitor, in dictating pancreatic carcinoma subcutaneous ferroptotic death. Taken together, our findings reveal a new role of the H/NS microenvironment against ferroptosis and suggest a potential therapeutic strategy for overcoming ferroptosis resistance in pancreatic cancer cells.