Ectosomal PKM2 Promotes HCC by Inducing Macrophage Differentiation and Remodeling the Tumor Microenvironment

Hou, Peipei; Luo, Lijuan; Chen, Hang-zi; Chen, Qi-Tao; Bian, Xueli; Wu, Sheng-fu; Zhou, Jiaxin; Zhao, Wenxiu; Liu, Jianming; Wang, Xiaomin; Zhang, Zhiyuan; Yao, Luming; Chen, Qinghua; Zhou, Dawang; Wu, Qiao

doi:10.1016/j.molcel.2020.05.004

Cited by 136 publications

(117 citation statements)

References 54 publications

(67 reference statements)

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“…Peptide SMIM30 promotes HCC development by inducing SRC/YES1 membrane anchoring and MAPK pathway activation [17]. Ectosomal PKM2 promotes HCC by inducing macrophage differentiation and remodeling the tumor microenvironment [18]. And the prognostic model composed of multiple genes can better predict the OS in HCC patients [13].…”

Section: Discussionmentioning

confidence: 99%

A genomic-clinicopathologic nomogram for predicting overall survival of hepatocellular carcinoma

Zhou

Cai

2020

BMC Cancer

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Background Hepatocellular carcinoma (HCC) is a common digestive tumor with great heterogeneity and different overall survival (OS) time, causing stern problems for selecting optimal treatment. Here we aim to establish a nomogram to predict the OS in HCC patients. Methods International Cancer Genome Consortium (ICGC) database was searched for the target information in our study. Lasso regression, univariate and multivariate cox analysis were applied during the analysis process. And a nomogram integrating model scoring and clinical characteristic was drawn. Results Six mRNAs were screened out by Lasso regression to make a model for predicting the OS of HCC patients. And this model was proved to be an independent prognostic model predicting OS in HCC patients. The area under the ROC curve (AUC) of this model was 0.803. TCGA database validated the significant value of this 6-mRNA model. Eventually a nomogram including 6-mRNA risk score, gender, age, tumor stage and prior malignancy was set up to predict the OS in HCC patients. Conclusions We established an independent prognostic model of predicting OS for 1–3 years in HCC patients, which is available to all populations. And we developed a nomogram on the basis of this model, which could be of great help to precisely individual treatment measures.

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Section: Discussionmentioning

confidence: 99%

A genomic-clinicopathologic nomogram for predicting overall survival of hepatocellular carcinoma

Zhou

Cai

2020

BMC Cancer

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“…This is mediated by ARRDC1 and ARRDC4, which independently stimulate ARMM formation [Mackenzie et al., 2016]. Interestingly, selective targeting to ARMMs may not be limited to membrane proteins because hepatocellular carcinoma‐derived ectosomes contain the pyruvate kinase M2 (PKM2) isoform, an enzyme which catalyses the final step of glycolysis and is highly expressed in cancer cells [Hou et al., 2020]. The sorting mechanism of this soluble enzyme to ARMMs is not yet deciphered, but it depends on prior sumoylation as well as on ARRDC1, with whom PKM2 interacts.…”

Section: New Functions Of Arrdcs In Intercellular Communication Throumentioning

confidence: 99%

The α‐arrestin family of ubiquitin ligase adaptors links metabolism with selective endocytosis

Kahlhofer¹,

Léon

Teis³

et al. 2021

Biology of the Cell

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The regulation of nutrient uptake into cells is important, as it allows to either increase biomass for cell growth or to preserve homoeostasis. A key strategy to adjust cellular nutrient uptake is the reconfiguration of the nutrient transporter repertoire at the plasma membrane by the addition of nutrient transporters through the secretory pathway and by their endocytic removal. In this review, we focus on the mechanisms that regulate selective nutrient transporter endocytosis, which is mediated by the α‐arrestin protein family. In the budding yeast Saccharomyces cerevisiae, 14 different α‐arrestins (also named arrestin‐related trafficking adaptors, ARTs) function as adaptors for the ubiquitin ligase Rsp5. They instruct Rsp5 to ubiquitinate subsets of nutrient transporters to orchestrate their endocytosis. The ART proteins are under multilevel control of the major nutrient sensing systems, including amino acid sensing by the general amino acid control and target of rapamycin pathways, and energy sensing by 5′‐adenosine‐monophosphate‐dependent kinase. The function of the six human α‐arrestins is comparably under‐characterised. Here, we summarise the current knowledge about the function, regulation and substrates of yeast ARTs and human α‐arrestins, and highlight emerging communalities and general principles.

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“…On the other hand, some proteins in TEXs can partially reflect the dysregulated protein profile in tumor cells, reveal the characteristics of tumor cells, and provide a new direction for the diagnosis or prognostic evaluation of tumors 12,13 . Numerous recent studies have confirmed that exosomes play a vital role in the progression of HCC [14][15][16][17][18] .…”

Section: Introductionmentioning

confidence: 96%

Exosome-derived ENO1 regulates integrin α6β4 expression and promotes hepatocellular carcinoma growth and metastasis

et al. 2020

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Alpha-enolase (ENO1) has been found to be dysregulated in several human malignancies, including hepatocellular carcinoma (HCC). Although the role of ENO1 as a glycolytic enzyme in HCC cells has been well characterized, little is known about the other roles of ENO1, especially exosome-derived ENO1, in regulating HCC progression. Here, we demonstrated that ENO1 is frequently upregulated in HCC cells or tissues, with even higher expression in highly metastatic HCC cells or metastatic tissues as well as in exosomes derived from highly metastatic sources. Moreover, ENO1 expression is associated with the tumor-node-metastasis (TNM) stage, differentiation grade and poor prognosis in HCC patients. Surprisingly, ENO1 can be transferred between HCC cells via exosome-mediated crosstalk, exhibiting an effect similar to that of ENO1 overexpression in HCC cells, which promoted the growth and metastasis of HCC cells with low ENO1 expression by upregulating integrin α6β4 expression and activating the FAK/Src-p38MAPK pathway. In summary, our data suggest that exosome-derived ENO1 is essential to promoting HCC growth, metastasis, and further patient deterioration. The findings from this study implicate a novel biomarker for the clinical evaluation of HCC progression, especially the prediction of HCC metastatic risk.

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Ectosomal PKM2 Promotes HCC by Inducing Macrophage Differentiation and Remodeling the Tumor Microenvironment

Cited by 136 publications

References 54 publications

A genomic-clinicopathologic nomogram for predicting overall survival of hepatocellular carcinoma

A genomic-clinicopathologic nomogram for predicting overall survival of hepatocellular carcinoma

The α‐arrestin family of ubiquitin ligase adaptors links metabolism with selective endocytosis

Exosome-derived ENO1 regulates integrin α6β4 expression and promotes hepatocellular carcinoma growth and metastasis

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