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

被引：44

作者：

Dhanasekaran, Renumathy ^{[1
]}

Baylot, Virginie ^{[2
,3
]}

Kim, Minsoon ^{[2
,3
]}

Kuruvilla, Sibu ^{[2
,3
]}

Bellovin, David, I ^{[2
,3
]}

Adeniji, Nia ^{[2
,3
]}

Rajan, Anand ^{[4
]}

Lai, Ian ^{[2
,3
]}

Gabay, Meital ^{[2
,3
]}

Tong, Ling ^{[2
,3
]}

Krishnan, Maya ^{[2
,3
]}

Park, Jangho ^{[2
,3
]}

Hu, Theodore ^{[2
,3
]}

Barbhuiya, Mustafa A. ^{[5
,6
,7
,8
]}

Gentles, Andrew J. ^{[9
,10
]}

Kannan, Kasthuri ^{[11
,12
]}

Tran, Phuoc T. ^{[5
,6
,7
,8
]}

Felsher, Dean W. ^{[2
,3
]}

机构：

[1] Stanford Univ, Div Gastroenterol & Hepatol, Stanford, CA 94305 USA

[2] Stanford Univ, Dept Med, Div Oncol, Stanford, CA 94305 USA

[3] Stanford Univ, Dept Pathol, Div Oncol, Stanford, CA 94305 USA

[4] Univ Iowa Hosp & Clin, Dept Pathol, Iowa City, IA 52242 USA

[5] Johns Hopkins Univ, Radiat Oncol & Mol Radiat Sci, Baltimore, MD USA

[6] Johns Hopkins Univ, Sch Med, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA

[7] Johns Hopkins Univ, Sch Med, James Buchanan Brady Urol Inst, Baltimore, MD USA

[8] Johns Hopkins Univ, Sch Med, Dept Urol, Baltimore, MD 21205 USA

[9] Stanford Univ, Sch Med, Dept Med Biomed Informat, Stanford, CA USA

[10] Stanford Univ, Sch Med, Dept Biomed Data Sci, Stanford, CA USA

[11] NYU Langone Med Ctr, Dept Pathol, New York, NY USA

[12] NYU Langone Med Ctr, Genome Technol Ctr, New York, NY USA

来源：

ELIFE | 2020年 / 9卷

关键词：

GENE-EXPRESSION; TRANSCRIPTION FACTOR; MONOCLONAL-ANTIBODY; TUMOR PROGRESSION; MACROPHAGES; CELLS; DIFFERENTIATION; INITIATION; PLASTICITY; REGULATOR;

D O I：

10.7554/eLife.50731

中图分类号：

Q [生物科学];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：28

共 57 条

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