Dishevelled-3 phosphorylation is governed by HIPK2/PP1C α/ITCH axis and the non-phosphorylated form promotes cancer stemness via LGR5 in hepatocellular carcinoma.

In this study, we showed that Dvl3 was significantly overexpressed in human hepatocellular carcinomas (HCCs) and promoted cancer stemness both in vitro and in vivo. We found that the non-phosphorylated (NP)-Dvl3 was more stable than the phosphorylated form, more active in activating β-catenin transcriptional activity, and more potent in enhancing self-renewal ability in HCC cells. Mechanistically, we confirmed that the homeodomain-interacting protein kinase-2 (HIPK2) and E3 ubiquitin ligase ITCH were able to physically bind to Dvl3 protein. Knockdown of HIPK2 and the protein phosphatase regulatory unit C-alpha (PP1Cα) resulted in sustained Dvl3 phosphorylation and hence decrease in the NP form of Dvl3. On the other hand, knockdown of E3 ubiquitin ligase ITCH reduced the phosphorylation-induced degradation and stabilized the phosphorylated Dvl3 protein. Furthermore, the NP-Dvl3 enhanced the LGR5 promoter activity to upregulate LGR5 expression, which was associated with increased cancer stemness in HCC. Our findings established that HIPK2/PP1Cα/ITCH axis sustains the de-phosphorylation of Dvl3. This post-translational modification of Dvl3 in turn maintains LGR5 expression and enhances the cancer stemness properties in HCC. PMID: 28455968 [PubMed - as supplied by publisher]
Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Related Links:

Publication date: Available online 2 April 2020Source: The Journal of Molecular DiagnosticsAuthor(s): Stefan Schmidt, Annett Linge, Marianne Großer, Fabian Lohaus, Volker Gudziol, Alexander Nowak, Ingeborg Tinhofer, Volker Budach, Ali Sak, Martin Stuschke, Panagiotis Balermpas, Claus Rödel, Henning Schäfer, Anca-Ligia Grosu, Amir Abdollahi, Jürgen Debus, Ute Ganswindt, Claus Belka, Steffi Pigorsch, Stephanie E. Combs
Source: The Journal of Molecular Diagnostics - Category: Pathology Source Type: research
Authors: Peng Y, Wei Q, He Y, Xie Q, Liang Y, Zhang L, Xia Y, Li Y, Chen W, Zhao J, Chai J Abstract Introduction: Hepatocellular carcinoma (HCC) is an aggressive tumor type which results in poor prognosis. ALBI and Child-Pugh score have been widely applied for predicting prognosis in patients with liver diseases. We conducted a systematic review to compare the prognostic ability of ALBI versus Child-Pugh in HCC patients.Areas covered: PubMed, EMBASE and Cochrane Library were explored. The data were extracted from every study. Studies investigating HCC patients and comparing the predicting ability between ALBI and C...
Source: Expert Review of Gastroenterology and Hepatology - Category: Gastroenterology Tags: Expert Rev Gastroenterol Hepatol Source Type: research
CONCLUSIONS: Our findings support the protective effect a normal weight against advanced adenomas. Reduction of BMI value should be pursued in healthy programs. PMID: 32233893 [PubMed - as supplied by publisher]
Source: Scandinavian Journal of Gastroenterology - Category: Gastroenterology Tags: Scand J Gastroenterol Source Type: research
Conclusion: There is a slightly increasing trend in the occurrence of esophageal perforations. Contemporary treatment is less invasive with similar results. Patients treated in high-volume hospitals have better prognosis. PMID: 32233883 [PubMed - as supplied by publisher]
Source: Scandinavian Journal of Gastroenterology - Category: Gastroenterology Tags: Scand J Gastroenterol Source Type: research
This study verified that MafF acted as a tumorsuppressor in HCC and revealed the upstream regulation mechanism of MafF, which provided anew perspective for potential therapeutic targets of HCC. PMID: 31969212 [PubMed - as supplied by publisher]
Source: Oncology Research - Category: Cancer & Oncology Tags: Oncol Res Source Type: research
Conclusion The elucidation of the function of circRNAs is an emerging field of science with a tremendous potential after previously being dismissed as RNA artifacts. They are ubiquitously expressed and thousands of members have already been identified. This fact only expands their potential to possibly enhance our knowledge to understand the difference between health and disease. Owing to their structure stability and their presence in exosomes circRNAs may also exert their function in an autocrine, paracrine and possible endocrine fashion. In addition, the fact that circRNAs are widely distributed in the cellular compart...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
Authors: Guo W, Zhang J, Zhang D, Cao S, Li G, Zhang S, Wang Z, Wen P, Yang H, Shi X, Pan J, Ye H Abstract Hepatocellular carcinoma (HCC) ranks the sixth most common cancer and the third cause of cancer-related mortality worldwide. Recent studies identified that circ-ITCH Suppresses mutiple cancers proliferation via inhibiting the Wnt/beta-Catenin pathway. In current study, conducted a genetic association study together with epidemiological follow-up study to delineate the role of circ-ITCH in the development and progression of HCC. we found rs10485505 (adjusted OR =1.18; 95% CI=1.06-1.31; P value =3.1×10-3) ...
Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research
By Stacy SimonThe US Food and Drug Administration (FDA) has approved Keytruda (pembrolizumab) to treat people with head and neck squamous cell carcinoma that has spread or come back after previous chemotherapy treatment. It’s the first immunotherapy drug approved for head and neck cancer. Keytruda is already approved for melanoma and non-small cell lung cancer.The FDA based its approval on a clinical trial of 174 people with head and neck squamous cell carcinoma that had spread or come back after they were treated with platinum-based chemotherapy. Tumors shrank or disappeared in 16% of the participants who were given...
Source: American Cancer Society :: News and Features - Category: Cancer & Oncology Tags: Oral Cavity and Oropharyngeal Cancer Source Type: news
By Stacy SimonResults of a small clinical trial show that more than half the patients with Merkel cell carcinoma, a rare but aggressive type of skin cancer, improved when they took the immunotherapy drug Keytruda (pembrolizumab). And the improvement appears to be lasting longer than would be expected with standard treatment. This is a significant finding because there are currently no drugs that have been approved by the US Food and Drug Administration (FDA) to treat Merkel cell carcinoma. Researchers studying Keytruda and other drugs are trying to provide more treatment options for people with this type of skin cancer.Whi...
Source: American Cancer Society :: News and Features - Category: Cancer & Oncology Tags: Skin Cancer - Merkel Cell Source Type: news
In this study, we report that miR-411 expression is markedly upregulated in HCC cells and HCC tissues compared with normal control tissues and cells. Previous studies have shown that miR-411 plays a crucial role in a variety of biological processes in various human cancer cells. However, the specific function of miR-411 in HCC remains unclear. Ectopic expression of miR-411 promoted the proliferation and anchorage-independent growth of HCC cells, whereas inhibition of miR-411 reduced this effect. Bioinformatics analysis further revealed ITCH, a putative tumor suppressor as a potential target of miR-411. Data from luciferase...
Source: Biomedicine and pharmacotherapy = Biomedecine and pharmacotherapie - Category: Drugs & Pharmacology Authors: Tags: Biomed Pharmacother Source Type: research
More News: Cancer | Cancer & Oncology | Carcinoma | Hepatocellular Carcinoma | Itchiness | Liver Cancer | Study