Misshapen Disruption Cooperates with RasV12 to Drive Tumorigenesis

Kong, Du; Lu, Jin-Yu; Li, Xiaoqin; Zhao, Sihua; Xu, Wenyan; Fang, Jinan; Wang, Xing; Ma, Xianjue

doi:10.3390/cells10040894

Open AccessArticle

Misshapen Disruption Cooperates with Ras^V12 to Drive Tumorigenesis

by

Du Kong

^1,2,3,4,

Jin-Yu Lu

⁵,

Xiaoqin Li

^6,7,

Sihua Zhao

^2,3,4,

Wenyan Xu

^3,4,8

,

Jinan Fang

^2,3,4,

Xing Wang

^6,7,* and

Xianjue Ma

^1,2,3,4,*

¹

School of Medicine, Zhejiang University, Hangzhou 310058, China

²

Key Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou 310024, China

³

Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou 310024, China

⁴

Institute of Biology, Westlake Institute for Advanced Study, Hangzhou 310024, China

⁵

Baylor College of Medicine, Hematology & Oncology, Houston, TX 77054, USA

⁶

College of Resources and Environmental Sciences, China Agricultural University, Beijing 100193, China

⁷

Beijing Key Laboratory of Biodiversity and Organic Farming, Beijing 100193, China

⁸

Key Laboratory of Structural Biology of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou 310024, China

^*

Authors to whom correspondence should be addressed.

Cells 2021, 10(4), 894; https://doi.org/10.3390/cells10040894

Submission received: 24 February 2021 / Revised: 9 April 2021 / Accepted: 12 April 2021 / Published: 14 April 2021

(This article belongs to the Special Issue Research Advances in Invertebrate Experimental Models of Malignant Growth)

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Abstract

Although RAS family genes play essential roles in tumorigenesis, effective treatments targeting RAS-related tumors are lacking, partly because of an incomplete understanding of the complex signaling crosstalk within RAS-related tumors. Here, we performed a large-scale genetic screen in Drosophila eye imaginal discs and identified Misshapen (Msn) as a tumor suppressor that synergizes with oncogenic Ras (Ras^V12) to induce c-Jun N-terminal kinase (JNK) activation and Hippo inactivation, then subsequently leads to tumor overgrowth and invasion. Moreover, ectopic Msn expression activates Hippo signaling pathway and suppresses Hippo signaling disruption-induced overgrowth. Importantly, we further found that Msn acts downstream of protocadherin Fat (Ft) to regulate Hippo signaling. Finally, we identified msn as a Yki/Sd target gene that regulates Hippo pathway in a negative feedback manner. Together, our findings identified Msn as a tumor suppressor and provide a novel insight into RAS-related tumorigenesis that may be relevant to human cancer biology.

Keywords: Ras; Msn; Ft; Hippo; tumorigenesis; Drosophila

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MDPI and ACS Style

Kong, D.; Lu, J.-Y.; Li, X.; Zhao, S.; Xu, W.; Fang, J.; Wang, X.; Ma, X. Misshapen Disruption Cooperates with Ras^V12 to Drive Tumorigenesis. Cells 2021, 10, 894. https://doi.org/10.3390/cells10040894

AMA Style

Kong D, Lu J-Y, Li X, Zhao S, Xu W, Fang J, Wang X, Ma X. Misshapen Disruption Cooperates with Ras^V12 to Drive Tumorigenesis. Cells. 2021; 10(4):894. https://doi.org/10.3390/cells10040894

Chicago/Turabian Style

Kong, Du, Jin-Yu Lu, Xiaoqin Li, Sihua Zhao, Wenyan Xu, Jinan Fang, Xing Wang, and Xianjue Ma. 2021. "Misshapen Disruption Cooperates with Ras^V12 to Drive Tumorigenesis" Cells 10, no. 4: 894. https://doi.org/10.3390/cells10040894

APA Style

Kong, D., Lu, J.-Y., Li, X., Zhao, S., Xu, W., Fang, J., Wang, X., & Ma, X. (2021). Misshapen Disruption Cooperates with Ras^V12 to Drive Tumorigenesis. Cells, 10(4), 894. https://doi.org/10.3390/cells10040894

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Misshapen Disruption Cooperates with Ras^V12 to Drive Tumorigenesis

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