LY6/PLAUR domain containing 3 (LYPD3) maintains melanoma cell stemness and mediates an immunosuppressive microenvironment

Author:

Hu Yi-dou,Wu Ke,Liu Yuan-jie,Zhang Qian,Shen Hui,Ji Jin,Fang Dong,Xi Song-yang

Abstract

Abstract Background Malignant melanoma is a highly heterogeneous skin cancer with the highest mortality rate among dermatological cancers. Catenins form functional networks in the nucleus to regulate gene expression and determine cell fate. Dysregulation of catenin expression correlates with the malignant characteristics of the tumor. We aimed to investigate the regulatory mechanisms of catenins in melanoma and to further define the function of catenin-related molecular signaling in the tumor microenvironment. Methods In this study, a bioinformatics approach combined with experimental validation was used to explore the potential tumor biology mechanisms of catenin-related signaling. Results Melanoma patients can be divided into two catenin clusters. Patients defined by high Junction Plakoglobin (JUP), Plakophilin 1 (PKP1), Plakophilin 3 (PKP3) levels (C2) had shorter survival time than other patients (C1). We demonstrated that JUP regulates Anterior Gradient 2 (AGR2)/LY6/PLAUR Domain Containing 3 (LYPD3) to maintain melanoma stemness and promotes glycolysis. We also found that LYPD3 was co-expressed with S100A9 and associated with immunosuppressive tumor microenvironment (TME). Conclusion The JUP/AGR2/LYPD3 signaling axis plays an important role in the malignant features of melanoma. Targeting the JUP/AGR2/LYPD3 signaling axis can help develop promising drugs.

Funder

Youth Science and Technology Project of Zhangjiagang

Social Development Guiding Science and Technology Plan Project of Zhenjiang

Science and Technology Project of Jiangsu Provincial Administration of Traditional Chinese Medicine

Suzhou Science and Education Promotion Health Project

Talent and Technology Construction Fund Project of Zhenjiang Hospital of Chinese Traditional and Western Medicine

Publisher

Springer Science and Business Media LLC

Subject

Applied Mathematics,General Agricultural and Biological Sciences,General Biochemistry, Genetics and Molecular Biology,Modeling and Simulation,Ecology, Evolution, Behavior and Systematics,Immunology

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