| First Author | Dhanasekaran R | Year | 2020 |
| Journal | Elife | Volume | 9 |
| PubMed ID | 31933479 | Mgi Jnum | J:283336 |
| Mgi Id | MGI:6388332 | Doi | 10.7554/eLife.50731 |
| Citation | Dhanasekaran R, et al. (2020) MYC and Twist1 cooperate to drive metastasis by eliciting crosstalk between cancer and innate immunity. Elife 9:e50731 |
| abstractText | Metastasis is a major cause of cancer mortality. We generated an autochthonous transgenic mouse model whereby conditional expression of MYC and Twist1 enables hepatocellular carcinoma (HCC) to metastasize in >90% of mice. MYC and Twist1 cooperate and their sustained expression is required to elicit a transcriptional program associated with the activation of innate immunity, through secretion of a cytokinome that elicits recruitment and polarization of tumor associated macrophages (TAMs). Systemic treatment with Ccl2 and Il13 induced MYC-HCCs to metastasize; whereas, blockade of Ccl2 and Il13 abrogated MYC/Twist1-HCC metastasis. Further, in 33 human cancers (n = 9502) MYC and TWIST1 predict poor survival (p=4.3x10(-10)), CCL2/IL13 expression (p<10(-109)) and TAM infiltration (p<10(-96)). Finally, in the plasma of patients with HCC (n = 25) but not cirrhosis (n = 10), CCL2 and IL13 were increased and IL13 predicted invasive tumors. Therefore, MYC and TWIST1 generally appear to cooperate in human cancer to elicit a cytokinome that enables metastasis through crosstalk between cancer and immune microenvironment. |
