Wang, Haichuan and Wang, Pan and Xu, Meng and Song, Xinhua and Wu, Hong and Evert, Matthias and Calvisi, Diego F. and Zeng, Yong and Chen, Xin (2021) Distinct functions of transforming growth factor-beta signaling in c-MYC driven hepatocellular carcinoma initiation and progression. CELL DEATH & DISEASE, 12 (2): 200. ISSN 2041-4889,
Full text not available from this repository. (Request a copy)Abstract
Dysregulation of transforming growth factor-beta (TGF beta) signaling has been implicated in liver carcinogenesis with both tumor promoting and inhibiting activities. Activation of the c-MYC protooncogene is another critical genetic event in hepatocellular carcinoma (HCC). However, the precise functional crosstalk between c-MYC and TGF beta signaling pathways remains unclear. In the present investigation, we investigated the expression of TGF beta signaling in c-MYC amplified human HCC samples as well as the mechanisms whereby TGF beta modulates c-Myc driven hepatocarcinogenesis during initiation and progression. We found that several TGF beta target genes are overexpressed in human HCCs with c-MYC amplification. In vivo, activation of TGF beta 1 impaired c-Myc murine HCC initiation, whereas inhibition of TGF beta pathway accelerated this process. In contrast, overexpression of TGF beta 1 enhanced c-Myc HCC progression by promoting tumor cell metastasis. Mechanistically, activation of TGF beta promoted tumor microenvironment reprogramming rather than inducing epithelial-to-mesenchymal transition during HCC progression. Moreover, we identified PMEPA1 as a potential TGF beta 1 target. Altogether, our data underline the divergent roles of TGF beta signaling during c-MYC induced HCC initiation and progression.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | EPITHELIAL-MESENCHYMAL TRANSITION; TGF-BETA; EXPRESSION; METASTASIS; EMT; MICROENVIRONMENT; HEPATOCYTES; BIOMARKERS; INDUCTION; CATENIN; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Pathologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 23 Sep 2022 05:18 |
| Last Modified: | 23 Sep 2022 05:18 |
| URI: | https://pred.uni-regensburg.de/id/eprint/47893 |
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