DataVXAdvanced SciencePaper
journal article·2023-09Open access

eIF3f Mediates SGOC Pathway Reprogramming by Enhancing Deubiquitinating Activity in Colorectal Cancer

Qihao Pan, Fenghai Yu, Huilin Jin, Peng Zhang, Xiaoling Huang, Jingxuan Peng, Xiaoshan Xie, Xiangli Li, Ning Ma, Yue Wei, Weijie Wen, Jieping Zhang, Boyu Zhang, Hongyan Yu, Yuanxun Xiao, Ran‐yi Liu, Qingxin Liu, Xiangqi Meng, Mong‐Hong Lee

Advanced Science· Volume 10· Issue 27
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Source abstract

Abstract

Abstract Numerous studies have demonstrated that individual proteins can moonlight. Eukaryotic Initiation translation factor 3, f subunit (eIF3f) is involved in critical biological functions; however, its role independent of protein translation in regulating colorectal cancer (CRC) is not characterized. Here, it is demonstrated that eIF3f is upregulated in CRC tumor tissues and that both Wnt and EGF signaling pathways are participating in eIF3f's oncogenic impact on targeting phosphoglycerate dehydrogenase (PHGDH) during CRC development. Mechanistically, EGF blocks FBXW7β‐mediated PHGDH ubiquitination through GSK3β deactivation, and eIF3f antagonizes FBXW7β‐mediated PHGDH ubiquitination through its deubiquitinating activity. Additionally, Wnt signals transcriptionally activate the expression of eIF3f, which also exerts its deubiquitinating activity toward MYC, thereby increasing MYC‐mediated PHGDH transcription. Thereby, both impacts allow eIF3f to elevate the expression of PHGDH, enhancing Serine–Glycine–One–Carbon (SGOC) signaling pathway to facilitate CRC development. In summary, the study uncovers the intrinsic role and underlying molecular mechanism of eIF3f in SGOC signaling, providing novel insight into the strategies to target eIF3f‐PHGDH axis in CRC.
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Research context

OpenAlex topics: Biochemical and Molecular Research · Cancer, Hypoxia, and Metabolism · Cancer Research and Treatments

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Department of General Surgery The Sixth Affiliated Hospital Sun Yat‐sen University Guangzhou 510655 China

Guangdong Provincial Key laboratory of Colorectal and Pelvic Floor Diseases The Sixth Affiliated Hospital Sun Yat‐sen University Guangzhou 510655 China

Biomedical Innovation Center The Sixth Affiliated Hospital Sun Yat‐sen University Guangzhou 510655 China

Department of Obstetrics and Gynecology The Sixth Affiliated Hospital Sun Yat‐sen University Guangzhou 510655 China

Department of Clinical Biological Resource Bank Guangzhou Institute of Pediatrics Guangzhou Women and Children's Medical Center Guangzhou Medical University Guangzhou 510623 China

Burn Plastic Surgery Yue bei People's Hospital Wujiang 512099 China

State Key Laboratory of Oncology in South China & Collaborative Innovation Center of Cancer Medicine Sun Yat‐sen University Cancer Center Guangzhou 510060 China

Department of Oncology The Sixth Affiliated Hospital Sun Yat‐sen University Guangzhou 510655 China

Funding

National Natural Science Foundation of China · Natural Science Foundation of Guangdong Province

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