Dowejko, Albert and Bauer, Richard and Bauer, Karin and Mueller-Richter, Urs D. A. and Reichert, Torsten E. (2012) The human HECA interacts with cyclins and CDKs to antagonize Wnt-mediated proliferation and chemoresistance of head and neck cancer cells. EXPERIMENTAL CELL RESEARCH, 318 (5). pp. 489-499. ISSN 0014-4827,
Full text not available from this repository. (Request a copy)Abstract
There is a growing evidence that the human homologue of the Drosophila headcase (HECA) plays an important role in human carcinogenesis. So far specific protein interaction partners and affected signaling pathways of HECA are still elusive. In a recent study we showed that HECA overexpression in oral squamous-cell carcinoma (OSCC) keratinocytes has tumor suppressive effects resulting in a recuperation of cell cycle control concerning the entry and progression of S-phase, G2- and M-phase. Currently, quantitative RT-PCR and immunohistochemical analysis of primary tumor tissue from OSCC patients demonstrate that HECA expression is markedly decreased compared to normal control patients with abundant HECA expression. Additionally, there is nearly no HECA expression in OSCC metastases. Here, we show that HECA expression is negatively controlled by the Wnt-pathway and TCF4, a Wnt related transcription factor, binds to the HECA promoter. Furthermore, immunocytochemistry reveals colocalization of HECA with the cyclin dependent kinase CDK9. Immunoprecipitation experiments and proximity ligation assays further reveal an interaction of HECA with CDK2, CDK9, Cyclin A and Cyclin K, a direct transcriptional target of the p53 tumor suppressor. Silencing HECA in OSCC cell lines leads to a significant increase of cell division and a markedly increased resistance against the chemotherapeutic cisplatin. On the contrary, HECA overexpressing OSCC cell lines show decreased resistance of OSCC cells against cisplatin. Therefore, HECA could be considered as future therapeutic agent against Wnt-dependent tumor progression. (C) 2011 Elsevier Inc. All rights reserved.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | REPLICATION STRESS-RESPONSE; SIGNALING PATHWAY; K FUNCTIONS; P-CADHERIN; CARCINOMA; TRANSCRIPTION; EXPRESSION; P53; ACTIVATION; COMPONENTS; Cell proliferation; Keratinocytes; OSCC, oral squamous-cell carcinoma; Human headcase; Wnt-signaling; Cell cycle control; Chemoresistance |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Mund-, Kiefer- und Gesichtschirurgie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 18 May 2020 09:05 |
| Last Modified: | 18 May 2020 09:05 |
| URI: | https://pred.uni-regensburg.de/id/eprint/19061 |
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