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

• Published in: eLife 2020-01, Vol.9
• Main Authors: Dhanasekaran, Renumathy, Baylot, Virginie, Kim, Minsoon, Kuruvilla, Sibu, Bellovin, David I, Adeniji, Nia, Rajan Kd, Anand, Lai, Ian, Gabay, Meital, Tong, Ling, Krishnan, Maya, Park, Jangho, Hu, Theodore, Barbhuiya, Mustafa A, Gentles, Andrew J, Kannan, Kasthuri, Tran, Phuoc T, Felsher, Dean W
• Format: Article
• Language: English
• Subjects: Analysis; Animal genetic engineering; Animals; Apoptosis; Cancer; Cancer Biology; Cancer cells; Cancer metastasis; Cancer prevention; Carcinoma; Cell Line, Tumor; Chemokine CCL2 - metabolism; Cirrhosis; Cytokines; Development and progression; Embryo; Epithelial-Mesenchymal Transition; Fibrosis - metabolism; Gene Expression Regulation, Neoplastic; Genes; Genetic engineering; Health aspects; Hepatocellular carcinoma; Humans; Immunity, Innate; Innate immunity; Interleukin 1; Interleukin 13; Interleukin-13 - metabolism; Invasiveness; Liver; Liver cancer; Liver cirrhosis; Lungs; Macrophages; Macrophages - immunology; Metastases; Metastasis; Mice; Mice, Transgenic; Monocyte chemoattractant protein 1; Mortality; MYC; Myc protein; Neoplasm Metastasis; Neoplasm Transplantation; Neoplasms - metabolism; Nuclear Proteins - metabolism; Principal Component Analysis; Prognosis; Proteins; Proto-Oncogene Proteins c-myc - metabolism; RAW 264.7 Cells; Rodents; Sequence Analysis, RNA; Signal Transduction; Transcription; Transcription factors; Transgenic animals; Transgenic mice; Tumor Microenvironment - physiology; Tumorigenesis; Tumors; Twist-Related Protein 1 - metabolism; Twist1
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/elife.50731

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