دورية أكاديمية
RASSF1A independence and early galectin‐1 upregulation in PIK3CA‐induced hepatocarcinogenesis: new therapeutic venues
| العنوان: | RASSF1A independence and early galectin‐1 upregulation in PIK3CA‐induced hepatocarcinogenesis: new therapeutic venues |
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| المؤلفون: | Alexander Scheiter, Katja Evert, Lucas Reibenspies, Antonio Cigliano, Katharina Annweiler, Karolina Müller, Laura‐Maria‐Giovanna Pöhmerer, Hongwei Xu, Guofei Cui, Timo Itzel, Silvia Materna‐Reichelt, Andrea Coluccio, Kamran Honarnejad, Andreas Teufel, Christoph Brochhausen, Frank Dombrowski, Xin Chen, Matthias Evert, Diego F. Calvisi, Kirsten Utpatel |
| المصدر: | Molecular Oncology, Vol 16, Iss 5, Pp 1091-1118 (2022) |
| بيانات النشر: | Wiley, 2022. |
| سنة النشر: | 2022 |
| المجموعة: | LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens |
| مصطلحات موضوعية: | alpelisib, galectin‐1, hepatocellular carcinoma, OTX008, SCD1, ZIP4, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282 |
| الوصف: | Aberrant activation of the phosphoinositide 3‐kinase (PI3K)/AKT/mTOR and Ras/mitogen‐activated protein kinase (MAPK) pathways is a hallmark of hepatocarcinogenesis. In a subset of hepatocellular carcinomas (HCCs), PI3K/AKT/mTOR signaling dysregulation depends on phosphatidylinositol‐4,5‐bisphosphate 3‐kinase, catalytic subunit alpha (PIK3CA) mutations, while RAS/MAPK activation is partly attributed to promoter methylation of the tumor suppressor Ras association domain‐containing protein 1 (RASSF1A). To evaluate a possible cocarcinogenic effect of PIK3CA activation and RASSF1A knockout, plasmids expressing oncogenic forms of PIK3CA (E545K or H1047R mutants) were delivered to the liver of RASSF1A knockout and wild‐type mice by hydrodynamic tail vein injection combined with sleeping beauty‐mediated somatic integration. Transfection of either PIK3CA E545K or H1047R mutants sufficed to induce HCCs in mice irrespective of RASSF1A mutational background. The related tumors displayed a lipogenic phenotype with upregulation of fatty acid synthase and stearoyl‐CoA desaturase‐1 (SCD1). Galectin‐1, which was commonly upregulated in preneoplastic lesions and tumors, emerged as a regulator of SCD1. Co‐inhibitory treatment with PIK3CA inhibitors and the galectin‐1 inhibitor OTX008 resulted in synergistic cytotoxicity in human HCC cell lines, suggesting novel therapeutic venues. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1878-0261 1574-7891 |
| Relation: | https://doaj.org/toc/1574-7891; https://doaj.org/toc/1878-0261 |
| DOI: | 10.1002/1878-0261.13135 |
| URL الوصول: | https://doaj.org/article/db2315a1864e41beaeb3a952e323cea0 |
| رقم الأكسشن: | edsdoj.b2315a1864e41beaeb3a952e323cea0 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 18780261 15747891 |
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| DOI: | 10.1002/1878-0261.13135 |