Genome-wide CRISPR/Cas9 library screening identified PHGDH as a critical driver for Sorafenib resistance in HCC

• Published in: Nature communications Vol. 10; no. 1; pp. 4681 - 13
• Main Authors: Wei, Lai, Lee, Derek, Law, Cheuk-Ting, Zhang, Misty Shuo, Shen, Jialing, Chin, Don Wai-Ching, Zhang, Allen, Tsang, Felice Ho-Ching, Wong, Ceci Lok-Sze, Ng, Irene Oi-Lin, Wong, Carmen Chak-Lui, Wong, Chun-Ming
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 15.10.2019; Nature Publishing Group; Nature Portfolio
• Subjects: 13/1; 13/106; 13/109; 13/2; 13/31; 13/44; 14/28; 38/22; 38/39; 38/77; 38/88; 38/91; 42/89; 49/47; 631/67; 631/67/1059; 631/67/1504; 631/67/1504/1610/4029; 631/67/2327; Antineoplastic Agents - therapeutic use; Apoptosis; Carcinoma, Hepatocellular - drug therapy; Carcinoma, Hepatocellular - genetics; Cell Line, Tumor; CRISPR; CRISPR-Cas Systems; Deactivation; Drug resistance; Drug Resistance, Neoplasm - genetics; Gene Knock-In Techniques; Gene Knockout Techniques; Genomes; Hepatocellular carcinoma; Humanities and Social Sciences; Humans; Inactivation; Inhibitor drugs; Kinases; Liver cancer; Liver Neoplasms - drug therapy; Liver Neoplasms - genetics; multidisciplinary; NADP; Phenylurea Compounds - therapeutic use; Phosphoglycerate dehydrogenase; Phosphoglycerate Dehydrogenase - antagonists & inhibitors; Phosphoglycerate Dehydrogenase - genetics; Protein-tyrosine kinase; Pyridines - therapeutic use; Quinolines - therapeutic use; Reactive Oxygen Species - metabolism; RNA-mediated interference; Science; Science (multidisciplinary); Screening; Serine; Sorafenib - therapeutic use; Targeted cancer therapy; Tyrosine

Sorafenib is the standard treatment for advanced hepatocellular carcinoma (HCC). However, the development of drug resistance is common. By using genome-wide CRISPR/Cas9 library screening, we identify phosphoglycerate dehydrogenase (PHGDH), the first committed enzyme in the serine synthesis pathway (...