Canopy Homolog 2 contributes to liver oncogenesis by promoting unfolded protein response–dependent destabilization of tumor protein P53

Hong, Feng; Lin, Chao Chun; Yan, Jinyue; Dong, Yizhou; Ouyang, Yuli; Kim, Doyeon; Zhang, Xiaoli; Liu, Bei; Sun, Shaoli; Gu, Wei; Li, Zihai

doi:10.1002/hep.32318

Cited by 10 publications

(6 citation statements)

References 41 publications

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“…Therefore, the quest for more effective ways to treat HCC is of great significance in improving the prognosis of HCC patients. Current studies have found that ERS is closely related to cell cycle regulation, activation and inhibition of proto-oncogenes and tumor suppressor genes, immune response, and changes in the tumor microenvironment during the occurrence and progression of HCC [106][107][108][109]. A recent study by Feng et al suggests that ERS in HCC cells can induce CNYP2, thereby activating three response pathways of UPR, inhibiting the expression of tumor suppressor gene p53 and shortening the cell cycle, ultimately promoting the occurrence of HCC [106].…”

Section: Liver Cancermentioning

confidence: 99%

“…Current studies have found that ERS is closely related to cell cycle regulation, activation and inhibition of proto-oncogenes and tumor suppressor genes, immune response, and changes in the tumor microenvironment during the occurrence and progression of HCC [106][107][108][109]. A recent study by Feng et al suggests that ERS in HCC cells can induce CNYP2, thereby activating three response pathways of UPR, inhibiting the expression of tumor suppressor gene p53 and shortening the cell cycle, ultimately promoting the occurrence of HCC [106]. Another study showed that ERS, when activated in liver cancer tissue, helps HCC cells to deliver exosome microRNA-23a-3p to macrophages, activate the PI3K-AKT pathway by inhibiting phosphatase and tensin homolog, and increase the expression of programmed death ligand 1.…”

Section: Liver Cancermentioning

confidence: 99%

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Endoplasmic reticulum stress-mediated cell death in liver injury

et al. 2022

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The endoplasmic reticulum is an important intracellular organelle that plays an important role in maintaining cellular homeostasis. Endoplasmic reticulum stress (ERS) and unfolded protein response (UPR) are induced when the body is exposed to adverse external stimuli. It has been established that ERS can induce different cell death modes, including autophagy, apoptosis, ferroptosis, and pyroptosis, through three major transmembrane receptors on the ER membrane, including inositol requirement enzyme 1α, protein kinase-like endoplasmic reticulum kinase and activating transcription factor 6. These different modes of cell death play an important role in the occurrence and development of various diseases, such as neurodegenerative diseases, inflammation, metabolic diseases, and liver injury. As the largest metabolic organ, the liver is rich in enzymes, carries out different functions such as metabolism and secretion, and is the body’s main site of protein synthesis. Accordingly, a well-developed endoplasmic reticulum system is present in hepatocytes to help the liver perform its physiological functions. Current evidence suggests that ERS is closely related to different stages of liver injury, and the death of hepatocytes caused by ERS may be key in liver injury. In addition, an increasing body of evidence suggests that modulating ERS has great potential for treating the liver injury. This article provided a comprehensive overview of the relationship between ERS and four types of cell death. Moreover, we discussed the mechanism of ERS and UPR in different liver injuries and their potential therapeutic strategies.

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Section: Liver Cancermentioning

confidence: 99%

Section: Liver Cancermentioning

confidence: 99%

Endoplasmic reticulum stress-mediated cell death in liver injury

et al. 2022

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“…This change indicated that FGF21 is an independent indicator of genetic hepatocarcinogenesis, but its expression is not a direct genetic marker of hepatoma cells per se 91 . Instead, a study showed that canopy homolog 2 promoted liver oncogenesis via destabilizing p53 and activating hepatic FGF21 expression 92 . Consistently, tumor suppressor miR-22 reduced hepatic FGFR1 by direct targeting and inhibited FGF21 expression by reducing its synthesis process 93 .…”

Section: Fgf21 Is a Promising Biomarker With Pleiotropic Activities I...mentioning

confidence: 99%

Hepatic FGF21: Its Emerging Role in Inter-Organ Crosstalk and Cancers

Sui

Chen

2022

Int. J. Biol. Sci.

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Fibroblast growth factor (FGF) 21 is one of the FGF members with special endocrine properties. In the last twenty years, it has attracted intense research and development for its physiological functions that respond to dietary manipulation, pharmacological benefits of improving the macronutrient metabolism, and clinical values as a biomarker of various human diseases. Generally, FGF21 can be produced by major metabolic organs, but only the subgroup from the liver shows canonical endocrine properties, which emphasizes the special value of delineating the unique secretory and functional characteristics of hepatic FGF21. There has been a growth in literature to address the extra-hepatic activities of FGF21, and many striking findings have therefore been published. Yet, they are fragmented and scattered, and controversies are raised from divergent findings. For this reason, there is a need for a systematic and critical evaluation of current research in this aspect. In this review, we focus on the current knowledge about the molecular biology of endocrine FGF21, especially present details on the regulation of circulating levels of FGF21. We also emphasize its emerging roles in inter-organ crosstalk and cancer development.

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“…One of the adaptive response is the UPR. In tumors, upregulation of UPR significantly increased the proliferation rate through destabilization of antitumor protein [6] , promotion of oncogene transcription and angiogenesis [7] . In addition, UPR is also responsible for immune evasion via upregulating PD-L1 or MICA/B expression [8,9] , facilitating the production of pro-inflammatory and immunomodulatory cytokines, such as interleukin-8 (IL-8), CXC-chemokine ligand 1 (CXCL1) and so on [10] .…”

Section: Introductionmentioning

confidence: 99%

Systematic Analysis of the Aberrances and Functional Implications of UPR in Hepatocellular Carcinoma

Huang

Gao

et al. 2023

Preprint

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Background Unfolded protein response (UPR), an orchestrating adaptive mechanism activated by endoplasmic reticulum (ER) stress, plays an instrumental protumoral roles in several kinds of cancers, and high unfolded protein response is correlated to poorer prognosis and malignant hallmark. Considerable evidence indicates that UPR induced by oncogenic conditions is a distinguishing feature of cancer. Methods Bioinformatics mining was carried out by using the public pancer data of TCGA and other public databases to analyze the differential gene expression profiles of the patients and Cox regression analysis to find out the differentially expressed endoplasmic reticulum stress related genes with prognostic value. ER-stress Potential Index (EPI) was defined to computationally dissect the UPR trends via gene set enrichment analysis using R package ‘GSVA’. Combined with TCGA and GEO databases, the clinical characteristics of EPI were comprehensively analyzed in LIHC. Virtual screening was performed to find out potential compounds targeting STC2, which was a good diagnostic marker and pharmacological target towards endoplasmic reticulum stress in LIHC. Results Pan-cancer analysis results showed that unfolded protein response pathway was generally positive associated with poor prognosis of patients across different cancer types. It would be an important and ubiquitous mechanism in different tumors. High EPI was positive associated with tumor malignant phenotype, including higher death rate, recurrence rate, metastatic risk, larger tumor size and other undesirable aggressive clinical traits. In addition, EPI was also responsible for immune evasion via upregulating the expression of immunosuppressive gene and facilitating the production of pro-inflammatory and immunomodulatory cytokines. Besides, EPI played pivotal role in liver cancers’ resistance of chemotherapy and therapeutic targeting UPR would be enhance the anti-tumor effectiveness. STC2 would be a good diagnostic marker and pharmacological target in LIHC. Through virtual screening, we found that flavonoids compounds could be a good compound targeting STC2. Flavonoids could become a good pharmaceutical therapeutic candidate in unique or adjuvant therapeutic approaches toward LIHC. Conclusion EPI was associated with subtypes and clinical features and providing new insight into tumor biology and can guide efficient pharmalogical intervention of unfolded protein response to help patients.

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Canopy Homolog 2 contributes to liver oncogenesis by promoting unfolded protein response–dependent destabilization of tumor protein P53

Cited by 10 publications

References 41 publications

Endoplasmic reticulum stress-mediated cell death in liver injury

Endoplasmic reticulum stress-mediated cell death in liver injury

Hepatic FGF21: Its Emerging Role in Inter-Organ Crosstalk and Cancers

Systematic Analysis of the Aberrances and Functional Implications of UPR in Hepatocellular Carcinoma

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