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

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

doi:10.1002/advs.202300759

Cited by 4 publications

(1 citation statement)

References 57 publications

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“…Our previous study proved that PHGDH expression in CRC cells could be restored by hsa_circ_0062682, which ultimately promoted serine metabolism and tumor growth in CRC[ 32 ]. Likewise, Pan et al [ 33 ] recently revealed that PHGDH can serve as a novel substrate for GSK3β/FBXW7β, and that eIF3f can enhance the serine one-carbon metabolic pathway to promote CRC progression by deubiquitinating PHGDH. In contrast, increased alcohol dehydrogenase 1C was found to reduce serine levels by simultaneously inhibiting the expression of PHGDH, thereby inhibiting the growth, migration, and invasion of CRC cells[ 34 ].…”

Section: Discussionmentioning

confidence: 99%

Global research trends and prospects of cellular metabolism in colorectal cancer

Liu,

Gong,

et al. 2024

World J Gastrointest Oncol

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BACKGROUND An increasing number of studies have focused on the role of cellular metabolism in the development of colorectal cancer (CRC). However, no work is currently available to synthesize the field through bibliometrics. AIM To analyze the development in the field of “glucose metabolism” (GM), “amino acid metabolism” (AM), “lipid metabolism” (LM), and “nucleotide metabolism” (NM) in CRC by visualization. METHODS Articles within the abovementioned areas of GM, AM, LM and NM in CRC, which were published from January 1, 1991, to December 31, 2022, are retrieved from the Web of Science Core Collection and analyzed by CiteSpace 6.2.R4 and VOSviewer 1.6.19. RESULTS The field of LM in CRC presented the largest number of annual publications and the fastest increase in the last decade compared with the other three fields. Meanwhile, China and the United States were two of the most prominent contributors in these four areas. In addition, Gang Wang, Wei Jia, Maria Notarnicola, and Cornelia Ulrich ranked first in publication numbers, while Jing-Yuan Fang, Senji Hirasawa, Wei Jia, and Charles Fuchs were the most cited authors on average in these four fields, respectively. “Gut microbiota” and “epithelial-mesenchymal transition” emerged as the newest burst words in GM, “gut microbiota” was the latest outburst word in AM, “metastasis”, “tumor microenvironment”, “fatty acid metabolism”, and “metabolic reprogramming” were the up-to-date outbreaking words in LM, while “epithelial-mesenchymal transition” and “apoptosis” were the most recently occurring words in NM. CONCLUSION Research in “cellular metabolism in CRC” is all the rage at the moment, and researchers are particularly interested in exploring the mechanism to explain the metabolic alterations in CRC. Targeting metabolic vulnerability appears to be a promising direction in CRC therapy.

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Section: Discussionmentioning

confidence: 99%

Global research trends and prospects of cellular metabolism in colorectal cancer

Liu,

Gong,

et al. 2024

World J Gastrointest Oncol

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The EIF3H-HAX1 axis increases RAF-MEK-ERK signaling activity to promote colorectal cancer progression

Jin,

Huang,

Pan

et al. 2024

Nat Commun

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Eukaryotic initiation translation factor 3 subunit h (EIF3H) plays critical roles in regulating translational initiation and predicts poor cancer prognosis, but the mechanism underlying EIF3H tumorigenesis remains to be further elucidated. Here, we report that EIF3H is overexpressed in colorectal cancer (CRC) and correlates with poor prognosis. Conditional Eif3h deletion suppresses colorectal tumorigenesis in AOM/DSS model. Mechanistically, EIF3H functions as a deubiquitinase for HAX1 and stabilizes HAX1 via antagonizing βTrCP-mediated ubiquitination, which enhances the interaction between RAF1, MEK1 and ERK1, thereby potentiating phosphorylation of ERK1/2. In addition, activation of Wnt/β-catenin signaling induces EIF3H expression. EIF3H/HAX1 axis promotes CRC tumorigenesis and metastasis in mouse orthotopic cancer model. Significantly, combined targeting Wnt and RAF1-ERK1/2 signaling synergistically inhibits tumor growth in EIF3H-high patient-derived xenografts. These results uncover the important roles of EIF3H in mediating CRC progression through regulating HAX1 and RAF1-ERK1/2 signaling. EIF3H represents a promising therapeutic target and prognostic marker in CRC.

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Classical swine fever virus inhibits serine metabolism-mediated antiviral immunity by deacetylating modified PHGDH

Li,

Huang,

Liu

et al. 2024

mBio

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Classical swine fever virus (CSFV), an obligate intracellular pathogen, hijacks cellular metabolism to evade immune surveillance and facilitate its replication. The precise mechanisms by which CSFV modulates immune metabolism remain largely unknown. Our study reveals that CSFV infection disrupts serine metabolism, which plays a crucial role in antiviral immunity. Notably, we discovered that CSFV infection leads to the deacetylation of PHGDH, a key enzyme in serine metabolism, resulting in autophagic degradation. This deacetylation impairs PHGDH’s enzymatic activity, reduces serine biosynthesis, weakens innate immunity, and promotes viral proliferation. Molecularly, CSFV infection induces the association of HDAC3 with PHGDH, leading to deacetylation at the K364 site. This modification attracts the E3 ubiquitin ligase RNF125, which facilitates the addition of K63-linked ubiquitin chains to PHGDH-K364R. Subsequently, PHGDH is targeted for lysosomal degradation by p62 and NDP52. Furthermore, the deacetylation of PHGDH disrupts its interaction with the NAD + substrate, destabilizing the PHGDH-NAD complex, impeding the active site, and thereby inhibiting de novo serine synthesis. Additionally, our research indicates that deacetylated PHGDH suppresses the mitochondria-MAVS-IRF3 pathway through its regulatory effect on serine metabolism, leading to decreased IFN-β production and enhanced viral replication. Overall, our findings elucidate the complex interplay between CSFV and serine metabolism, revealing a novel aspect of viral immune evasion through the lens of immune metabolism. IMPORTANCE Classical swine fever (CSF) seriously restricts the healthy development of China’s aquaculture industry, and the unclear pathogenic mechanism and pathogenesis of classical swine fever virus (CSFV) are the main obstacle to CSF prevention, control, and purification. Therefore, it is of great significance to explore the molecular mechanism of CSFV and host interplay, to search for the key signaling pathways and target molecules in the host that regulate the replication of CSFV infection, and to elucidate the mechanism of action of host immune dysfunction and immune escape due to CSFV infection for the development of novel CSFV vaccines and drugs. This study reveals the mechanism of serine metabolizing enzyme post-translational modifications and antiviral signaling proteins in the replication of CSFV and enriches the knowledge of CSFV infection and immune metabolism.

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

Cited by 4 publications

References 57 publications

Global research trends and prospects of cellular metabolism in colorectal cancer

Global research trends and prospects of cellular metabolism in colorectal cancer

The EIF3H-HAX1 axis increases RAF-MEK-ERK signaling activity to promote colorectal cancer progression

Classical swine fever virus inhibits serine metabolism-mediated antiviral immunity by deacetylating modified PHGDH

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