Uncovering and deciphering the pro-invasive role of HACE1 in melanoma cells

Hachem, Najla El; Habel, Nadia; Naiken, Tanesha; Bzioueche, Hanene; Chéli, Yann; Béranger, Guillaume E.; Jaune, Emilie; Rouaud, Florian; Nottet, Nicolas; Reinier, Frédéric; Gaudel, Céline; Colosetti, P.; Bertolotto, Corine; Ballotti, Robert

doi:10.1038/s41418-018-0090-y

Cited by 27 publications

(27 citation statements)

References 34 publications

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“…The results of the present study indicated that demethylation of the HACE1 promoter enhanced its expression, and inhibited proliferation and colony formation of liver cancer cells. However, a previous study demonstrated that HACE1 promotes melanoma cell migration and adhesion in vitro and that it is required for mouse lung colonization by melanoma cells in vivo (24). These findings indicated that whether HACE1 acts as a tumour suppressor gene or oncogene may depend on the cancer type.…”

Section: Discussionmentioning

confidence: 97%

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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Section: Discussionmentioning

confidence: 97%

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

Han

et al. 2019

Oncol Lett

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“…E-cadherin is a biomarker for cancer [ 18 , 40 ] and is attenuated and reduced in many cancers [ 41 – 43 ], especially in lung and breast cancers. E-cadherin loss in tumor cells leads to decreased adhesion between tumor cells, which favors epithelial-mesenchymal transition [ 44 ] and promotes the ability of tumor cells to invade and metastasize. In metastatic lung cancer (stages III and IV), E-cadherin protein levels were significantly lower than those in nonmetastatic stages (I and II).…”

Section: Discussionmentioning

confidence: 99%

LC-MS/MS-Based Quantitative Proteomics Analysis of Different Stages of Non-Small-Cell Lung Cancer

Zhou

Kong

Wang

et al. 2021

BioMed Research International

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Lung cancer has a higher incidence rate and mortality rate than all other cancers. Early diagnosis and treatment of lung cancer remain a major challenge, and the 5-year survival rate of its patients is only 15%. Basic and clinical research, especially the discovery of biomarkers, is crucial for improving the diagnosis and treatment of lung cancer patients. To identify novel biomarkers for lung cancer, we used the iTRAQ8-plex labeling technology combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS) to analyze the serum and urine of patients with different stages of lung adenocarcinoma and healthy individuals. A total of 441 proteins were identified in the serum, and 1,161 proteins were identified in the urine. The levels of elongation factor 1-alpha 2, proteasome subunit alpha type, and spermatogenesis-associated protein increased significantly in the serum of patients with lung cancer compared with those in healthy controls. The levels of transmembrane protein 143, cadherin 5, fibronectin 1, and collectin-11 decreased significantly in the serum of patients with metastases compared with those of nonmetastatic lung cancer patients. In the urine of stage III and IV lung cancer patients, the prostate-specific antigen and prostatic acid phosphatase decreased significantly, whereas neutrophil defensin 1 increased significantly. The results of LC-MS/MS were confirmed by enzyme-linked immunosorbent assay (ELISA) for transmembrane protein 143, cadherin 5, fibronectin 1, and collectin-11 in the serum. These proteins may be a potential early diagnosis and metastasis biomarkers for lung adenocarcinoma. Furthermore, the relative content of these markers in the serum and urine could be used to determine the progression of lung adenocarcinoma and achieve accurate staging and diagnosis.

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“…Even though HACE1 behaves as an anti-oncogene in most reports, its function in melanoma may be cell-specific tumorigenesis. HACE1 plays a pro-oncogenic role in melanoma by regulating fibronectin (FN) secretion and K27 ubiquitination of FN [24].…”

Section: Hace1mentioning

confidence: 99%

Ubiquitination and Deubiquitination in Melanoma Research and Clinically Relevant Outcomes

Guo¹,

Zhang²

2020

Ubiquitin - Proteasome Pathway

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Malignant melanoma is one of the most invasive tumors with increasing mortality, low overall survival rates and limited effective therapeutic strategies. Ubiquitination is a post-translational protein modification, which is regulated by a series of ubiquitination-associated enzymes. Ubiquitination plays a critical role in diverse pathophysiological activities of cellular and participates in the pathogenesis of various cancers, including melanoma. This study aims to provide a conclusive of ubiquitination and deubiquitination, and their potential clinical application value in melanoma in the following aspects: melanoma pathogenesis-related components and processes in the ubuiquitin-proteasome system (UPS), ubiquitination in melanoma immunological microenvironment modulation, ubiquitination of key transcription factors in melanoma and melanoma therapeutic strategy via targeting the UPS.

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Uncovering and deciphering the pro-invasive role of HACE1 in melanoma cells

Cited by 27 publications

References 34 publications

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

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

LC-MS/MS-Based Quantitative Proteomics Analysis of Different Stages of Non-Small-Cell Lung Cancer

Ubiquitination and Deubiquitination in Melanoma Research and Clinically Relevant Outcomes

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