HRC promotes anoikis resistance and metastasis by suppressing endoplasmic reticulum stress in hepatocellular carcinoma

Xia, Suhong; Wu, Jingwen; Zhou, Wangdong; Zhang, Mingyu; Zhao, Kai; Tian, Dean; Liu, Jingmei; Liao, Jiazhi

doi:10.7150/ijms.60610

Cited by 11 publications

(7 citation statements)

References 37 publications

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“…Then, these cells will be extruded by neighboring cells through mechanical force, and the extruded cells will undergo anoikis because of the lack of survival signals [ 28 – 30 ]. Some tumor cells themselves can resist anoikis by upregulating survival signals [ 31 ]. We speculate that if tumor cells of epithelial origin are extruded, they may continue to survive and even metastasize.…”

Section: Discussionmentioning

confidence: 99%

Cell adhesion molecule BVES functions as a suppressor of tumor cells extrusion in hepatocellular carcinoma metastasis

Han

Liu

et al. 2022

Cell Commun Signal

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Background Tumor cells detachment from primary lesions is an early event for hepatocellular carcinoma (HCC) metastasis, in which cell adhesion molecules play an important role. The role of mechanical crowding has attracted increasing attention. Previous studies have found that overcrowding can induce live cells extrusion to maintain epithelial cell homeostasis, and normally, live extruded cells eventually die through a process termed anoikis, suggesting the potential of tumor cells resistant to anoikis might initiate metastasis from primary tumors by cell extrusion. We have demonstrated transmembrane adhesion molecule blood vessel epicardial substance (BVES) suppression as an early event in HCC metastasis. However, whether its suppression is involved in HCC cell extrusion, especially in HCC metastasis, remains unknown. This study aims to investigate the role of BVES in tumor cells extrusion in HCC metastasis, as well as the underlying mechanisms. Methods Cells extrusion was observed by silicone chamber, petri dish inversion, and three-dimensional cell culture model. Polymerase chain reaction, western blotting, immunohistochemistry, immunofluorescence, co-immunoprecipitation, and RhoA activity assays were used to explore the underlying mechanisms of cell extrusion regulated by BVES. An orthotopic xenograft model was established to investigate the effects of BVES and cell extrusion in HCC metastasis in vivo. Results Tumor cell extrusion was observed in HCC cells and tissues. BVES expression was decreased both in HCC and extruded tumor cells. BVES overexpression led to the decrease in HCC cells extrusion in vitro and in vivo. Moreover, our data showed that BVES co-localized with ZO-1 and GEFT, regulating ZO-1 expression and localization, and GEFT distribution, thus modulating RhoA activity. Conclusion The present study revealed that BVES downregulation in HCC enhanced tumor cells extrusion, thus promoting HCC metastasis, which contributed to a more comprehensive understanding of tumor metastasis, and provided clues for developing novel HCC therapy strategies.

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Section: Discussionmentioning

confidence: 99%

Cell adhesion molecule BVES functions as a suppressor of tumor cells extrusion in hepatocellular carcinoma metastasis

Han

Liu

et al. 2022

Cell Commun Signal

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“…Multiple pathways can lead to the acquisition of anoikis resistance in HCC. Xia et al found that histidine-rich calcium binding protein (HRC) could enhance the anoikis resistance and promote the HCC metastasis via protein kinase RNA-like ER kinase (PERK)-eIF2a-ATF4-CHOP signaling axis [7]. Mo et al found that upregulation of IQGAP1 enhanced anoikis resistance, therefore promoting the migration and invasion of HCC cells [19].…”

Section: Discussionmentioning

confidence: 99%

“…As a special type of apoptosis induced by loss of correct cell adhesion, anoikis plays an important role in maintaining the normal integrity of tissues and participates in the invasion and metastasis of tumors, and anoikis resistance is often acquired during tumor progression [3][4][5][6]. A recent study showed that histidine-rich calcium binding protein (HRC) increased the anoikis resistance and promoted the HCC metastasis via the protein kinase RNA like ER kinase (PERK) -eIF2a-ATF4-CHOP signal pathway [7]. In another study, the ability of anoikis resistance of HCC cells was enhanced by inducing autophagy in the acidic environment of HCC, and autophagy inhibitors could reverse the effect of anoikis resistance [8].…”

Section: Introductionmentioning

confidence: 99%

A Anoikis-Related Risk Model: Predicts Prognosis and Immunotherapy Response for Hepatocellular Carcinoma

Ren

Kang

Yin

et al. 2022

Preprint

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Hepatocellular Carcinoma (HCC) is the leading cause of cancer-related deaths globally. Most HCC patients are already in advanced stages of the disease when a confirmed diagnosis was made with prone to metastasis and a poor prognosis. Anoikis resistance plays a critical role in tumor invasion and metastasis. whereas the role of anoikis in HCC remains unclear. According to univariate Cox regression and the least absolute shrinkage and selection operator (LASSO) analysis, anoikis-related genes (ARGs) associated with the overall rate (OS) were selected. Then, 3 prognostic ARGs (PDK4, STK11 and TFDP1) were identified by multivariate Cox regression, and to establish a risk model. According to the risk score, HCC patients were divided into high- and low-risk group. The OS rate and immune infiltration between two groups were evaluated by Kaplan-Meier, CIBERSORT and ssGSEA analysis. The OS rate of HCC patients in low-risk group was longer than that in the high-risk group. The results of nomogram showed that the ARGs prognostic signature was an independent prognostic predictor. In addition, consensus clustering analysis could cluster the patients into two subgroups with different immune infiltration. Besides, functional enrichment and drug sensitivity were also conducted between high- and low-risk groups. This study was the first to integrate multiple ARGs to establish a risk-predictive model, and might provide a new perspective for individualized and accurate therapy strategies for HCC patients.

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“…Similarly found by Suhong Xia et al that histidine-rich calcium-binding protein (HRC), an anoikis resistance-associated gene, was also overexpressed in LIHC patients and suggested that this promoted the metastasis of LIHC cells in vivo (Xia et al 2021). Therefore, deciphering the regulatory mechanisms of anoikis resistance would be helpful in improving the clinical management of LIHC.…”

Section: Introductionmentioning

confidence: 87%

An Anoikis-related LncRNA Signature: Integrated Analysis of Immune Infiltration Landscape in Patients with Liver Hepatocellular Carcinoma and Immunotherapy

Zhou¹,

Zhang²

2023

Preprint

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Liver hepatocellular carcinoma (LIHC) is one of the most common malignancies worldwide and any factor causing metastasis contributes to its poor prognosis. Long non-coding RNA (lncRNA) plays an important role in promoting the poor progression of LIHC. And the occurrence of anoikis resistance is also essential for tumor metastasis. The study aimed to establish an anoikis-related lncRNA (ARlncRNA) signature for LIHC. The raw data were obtained from the TCGA and GeneCards databases. Using the univariate Cox methods (p < 0.05) and the LASSO (10-fold cross-validation) regression analysis, we first identified a lncRNA-associated signature which consisted of AC100812.1, AL365295.1, AC073352.1, ELFN1-AS1, LINC00513, and MIR4435-2HG. Furthermore, we constructed a risk model based on the ARlncRNAs scores and evaluated it from different perspectives, including survival prognosis, clinical characteristics, signaling pathways, levels of immune cell infiltration, and drug sensitivity. The results of validation indicated that the prognostic performance of the lncRNA-associated risk score is excellent and is more suitable for constructing a prognostic model than other clinical features. We finally identified 3 LIHC subtypes and made predictions on their immune infiltration landscape and drug sensitivity. Our study elucidated the mechanisms of LIHC metastasis and its immune infiltration landscape, which was of great significance in expanding our understanding of LIHC progression and facilitating patients’ personalized management.

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HRC promotes anoikis resistance and metastasis by suppressing endoplasmic reticulum stress in hepatocellular carcinoma

Cited by 11 publications

References 37 publications

Cell adhesion molecule BVES functions as a suppressor of tumor cells extrusion in hepatocellular carcinoma metastasis

Cell adhesion molecule BVES functions as a suppressor of tumor cells extrusion in hepatocellular carcinoma metastasis

A Anoikis-Related Risk Model: Predicts Prognosis and Immunotherapy Response for Hepatocellular Carcinoma

An Anoikis-related LncRNA Signature: Integrated Analysis of Immune Infiltration Landscape in Patients with Liver Hepatocellular Carcinoma and Immunotherapy

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