MYC and Twist1 cooperate to drive metastasis by eliciting crosstalk between cancer and innate immunity

Metastasis is a major cause of cancer mortality. We generated an autochthonous transgenic mouse model whereby conditional expression of and enables hepatocellular carcinoma (HCC) to metastasize in >90% of mice. and 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 -HCCs to metastasize; whereas, blockade of Ccl2 and Il13 abrogated / -HCC metastasis. Further, in 33 human cancers (n = 9502) and predict poor survival (p=4.3×10 ), CCL2/IL13 expression (p