Overexpression of <scp>HACE</scp>1 in gastric cancer inhibits tumor aggressiveness by impeding cell proliferation and migration

Chen, Ying‐ling; Li, Dongping; Jiang, H.; Yang, Yang; Xu, Lili; Zhang, Shuncai; Gao, Hong

doi:10.1002/cam4.1496

Cited by 15 publications

(29 citation statements)

References 25 publications

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“…Finally, HECT E3 ubiquitin ligases are also involved in more rare cancers, such as gastric cancer, transitional cell carcinoma, esophageal squamous cell carcinoma (ESCC), pancreatic cancer and thyroid cancer. For example, HACE1 expression was shown to be suppressed in gastric cancer tissues, whereas its experimental overexpression can inhibit tumor proliferation, migration and enhance cell apoptosis (Chen et al, 2018). In contrast, NEDD4 expression is upregulated in advanced gastric cancer tissues, with a concurrent increased probability of metastasis (Ye et al, 2014).…”

Section: Cancersmentioning

confidence: 99%

HECT E3 ubiquitin ligases – emerging insights into their biological roles and disease relevance

Wang

Argiles-Castillo

Kane

et al. 2020

Journal of Cell Science

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Homologous to E6AP C-terminus (HECT) E3 ubiquitin ligases play a critical role in various cellular pathways, including but not limited to protein trafficking, subcellular localization, innate immune response, viral infections, DNA damage responses and apoptosis. To date, 28 HECT E3 ubiquitin ligases have been identified in humans, and recent studies have begun to reveal how these enzymes control various cellular pathways by catalyzing the post-translational attachment of ubiquitin to their respective substrates. New studies have identified substrates and/or interactors with different members of the HECT E3 ubiquitin ligase family, particularly for E6AP and members of the neuronal precursor cell-expressed developmentally downregulated 4 (NEDD4) family. However, there still remains many unanswered questions about the specific roles that each of the HECT E3 ubiquitin ligases have in maintaining cellular homeostasis. The present Review discusses our current understanding on the biological roles of the HECT E3 ubiquitin ligases in the cell and how they contribute to disease development. Expanded investigations on the molecular basis for how and why the HECT E3 ubiquitin ligases recognize and regulate their intracellular substrates will help to clarify the biochemical mechanisms employed by these important enzymes in ubiquitin biology.

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Section: Cancersmentioning

confidence: 99%

HECT E3 ubiquitin ligases – emerging insights into their biological roles and disease relevance

Wang

Argiles-Castillo

Kane

et al. 2020

Journal of Cell Science

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“…HACE1 downregulation has been identified in numerous types of cancer, including hepatocellular carcinoma, breast cancer, colorectal cancer, gastric cancer and leukaemia (5,11). Previous studies have demonstrated that decreased expression or deletion of HACE1 caused by HACE1 methylation or ubiquitination is associated with the occurrence and invasion of various types of carcinoma (18,(21)(22)(23).…”

Section: Discussionmentioning

confidence: 99%

“…HACE1 was first studied in Wilms' tumour and was later identified to be frequently lost or downregulated in a variety of tumours. Its role in tumour suppression has been extensively investigated, and a number of studies have indicated that HACE1 can restrain reactive oxygen species generation, control cell fate by regulating TNF receptor superfamily member 1A, and impede tumour growth by accelerating the ubiquitination of Rac family small GTPase 1 (11,25,26). Notably, it has been reported that HACE1 acts as a tumour suppressor by ubiquitinating OPTN, and that it activates selective autophagy (10).…”

Section: Discussionmentioning

confidence: 99%

“…HECT domain and ankyrin repeat containing E3 ubiquitin protein ligase 1 (HACE1) is a member of the HECT domain-containing E3 ligase family and was originally identified to be associated with the occurrence of Wilms' tumour (7). Furthermore, additional studies revealed that lower expression or mutations of HACE1 are associated with numerous types of human malignant tumours, including breast cancer, colorectal cancer, lung cancer, liver cancer, gastric cancer and lymphoma (5,(8)(9)(10)(11)(12), which suggests that HACE1 functions as a tumour suppressor. Additional research concerning HACE1 has focused on a variety of downstream pathways; for example, HACE1 has been reported to act as a tumour suppressor by ubiquitinating optineurin (OPTN) and activating selective autophagy (10).…”

Section: Introductionmentioning

confidence: 99%

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Demethylation of the HACE1 gene promoter inhibits the proliferation of human liver cancer cells

Han

et al. 2019

Oncol Lett

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HECT domain and ankyrin repeat containing E3 ubiquitin protein ligase 1 (HACE1) is frequently downregulated or lost in numerous types of cancer, including liver cancer. The aim of the present study was to examine whether demethylation of the HACE1 gene could inhibit tumour progression. The expression of HACE1 was detected in liver cancer cell lines. Clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated (Cas)-based demethylation single guide RNAs for the HACE1 gene promoter were designed and transfected into liver cancer cells. Subsequently, proliferation was detected by MTT and colony formation assays, and optineurin (OPTN) ubiquitination and microtubule-associated proteins 1A/1B light chain 3B protein levels were detected by immunoblotting. The levels of HACE1 were significantly reduced in liver cancer cell lines compared with in a normal liver cell line. Demethylation of the HACE1 gene promoter increased HACE1 expression, inhibited the proliferation of liver cancer cells, and promoted OPTN ubiquitination and autophagy activity in liver cancer cells. In conclusion, activation of HACE1 expression by promoter demethylation may provide a suitable approach for anticancer therapy.

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“…Thus, high levels of EPHA7 may have the effect of sequestering microRNAs and reducing proliferation in other cancers [31]. HACE1 is an E3 ligase downregulated in several cancers, including gastric cancer and breast cancer, and was found to inhibit the Wnt/β-catenin pathway, thereby playing a role in suppressing tumorigenesis [32, 33]. The pathway involving TRIP11 and triiodothyronine is necessary for localization of TRIP11 to the nucleus and was found to be disrupted in renal cell cancer, leading to progression [34].…”

Section: Discussionmentioning

confidence: 99%

An age-based, RNA expression paradigm for survival biomarker identification for pediatric neuroblastoma and acute lymphoblastic leukemia

et al. 2019

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Background Pediatric cancer survival rates overall have been improving, but neuroblastoma (NBL) and acute lymphoblastic leukemia (ALL), two of the more prevalent pediatric cancers, remain particularly challenging. One issue not yet fully addressed is distinctions attributable to age of diagnosis. Methods In this report, we verified a survival difference based on diagnostic age for both pediatric NBL and pediatric ALL datasets, with younger patients surviving longer for both diseases. We identified several gene expression markers that correlated with age, along a continuum, and then used a series of age-independent survival metrics to filter these initial correlations. Results For pediatric NBL, we identified 2 genes that are expressed at a higher level in lower surviving patients with an older diagnostic age; and 4 genes that are expressed at a higher level in longer surviving patients with a younger diagnostic age. For pediatric ALL, we identified 3 genes expressed at a higher level in lower surviving patients with an older diagnostic age; and 17 genes expressed at a higher level in longer surviving patients with a younger diagnostic age. Conclusions This process implicated pan-chromosome effects for chromosomes 11 and 17 in NBL; and for the X chromosome in ALL. Electronic supplementary material The online version of this article (10.1186/s12935-019-0790-5) contains supplementary material, which is available to authorized users.

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Overexpression of HACE1 in gastric cancer inhibits tumor aggressiveness by impeding cell proliferation and migration

Cited by 15 publications

References 25 publications

HECT E3 ubiquitin ligases – emerging insights into their biological roles and disease relevance

HECT E3 ubiquitin ligases – emerging insights into their biological roles and disease relevance

Demethylation of the HACE1 gene promoter inhibits the proliferation of human liver cancer cells

An age-based, RNA expression paradigm for survival biomarker identification for pediatric neuroblastoma and acute lymphoblastic leukemia

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