| First Author | Wang H | Year | 2021 |
| Journal | Cell Death Dis | Volume | 12 |
| Issue | 2 | Pages | 200 |
| PubMed ID | 33608500 | Mgi Jnum | J:314002 |
| Mgi Id | MGI:6805550 | Doi | 10.1038/s41419-021-03488-z |
| Citation | Wang H, et al. (2021) Distinct functions of transforming growth factor-beta signaling in c-MYC driven hepatocellular carcinoma initiation and progression. Cell Death Dis 12(2):200 |
| abstractText | Dysregulation of transforming growth factor-beta (TGFbeta) 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 TGFbeta signaling pathways remains unclear. In the present investigation, we investigated the expression of TGFbeta signaling in c-MYC amplified human HCC samples as well as the mechanisms whereby TGFbeta modulates c-Myc driven hepatocarcinogenesis during initiation and progression. We found that several TGFbeta target genes are overexpressed in human HCCs with c-MYC amplification. In vivo, activation of TGFbeta1 impaired c-Myc murine HCC initiation, whereas inhibition of TGFbeta pathway accelerated this process. In contrast, overexpression of TGFbeta1 enhanced c-Myc HCC progression by promoting tumor cell metastasis. Mechanistically, activation of TGFbeta promoted tumor microenvironment reprogramming rather than inducing epithelial-to-mesenchymal transition during HCC progression. Moreover, we identified PMEPA1 as a potential TGFbeta1 target. Altogether, our data underline the divergent roles of TGFbeta signaling during c-MYC induced HCC initiation and progression. |
