MYC and twist1 cooperate to drive metastasis by eliciting crosstalk between cancer and innate immunity

Renumathy Dhanasekaran, Virginie Baylot, Minsoon Kim, Sibu Kuruvilla, David I. Bellovin, Nia Adeniji, K. D. Anand Rajan, Ian Lai, Meital Gabay, Ling Tong, Maya Krishnan, Jangho Park, Theodore Hu, Mustafa A. Barbhuiya, Andrew J. Gentles, Kasthuri Kannan, Phuoc T. Tran, Dean W. Felsher

Research output: Contribution to journalArticlepeer-review

Abstract

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=4.3☓1010), CCL2/IL13 expression (p<10109) and TAM infiltration (p<1096). 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.

Original languageEnglish (US)
Article numbere50731
JournaleLife
Volume9
DOIs
StatePublished - Jan 2020

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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