DSCC1 interacts with HSP90AB1 and promotes the progression of lung adenocarcinoma via regulating ER stress

Cancer Cell International

Research

Huan-qi Zhang¹  Xu Lin²  Yuhong Yang²  Qingyi Zhang²  Jian Hu³  Qi Li⁴  Jun Deng⁴  Yang-ling Li⁵  Lin-wen Wu⁵  Chong Zhang⁶  Ye-han Liu⁷ 

[1] College of Pharmaceutical Sciences, Zhejiang University, 310058, Hangzhou, China;Department of Thoracic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, 310003, Hangzhou, China;Department of Thoracic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, 310003, Hangzhou, China;Cancer Center, Zhejiang University, 310058, Hangzhou, China;Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, 310006, Hangzhou, China;Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, 310006, Hangzhou, China;Department of Clinical Pharmacy, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, 310006, Hangzhou, China;School of Medicine, Hangzhou City University, No.51 Huzhou Street, 310015, Hangzhou, Zhejiang, China;School of Medicine, Hangzhou City University, No.51 Huzhou Street, 310015, Hangzhou, Zhejiang, China;College of Pharmaceutical Sciences, Zhejiang University, 310058, Hangzhou, China;

关键词: DSCC1;    HSP90AB1;    Lung adenocarcinoma;    PD-L1;    Proliferation;    Stemness;    Metastasis;   

DOI  :  10.1186/s12935-023-03047-w

 received in 2023-07-09, accepted in 2023-08-29,  发布年份 2023

来源: Springer

【 摘 要 】

Lung cancer is a leading cause of cancer-related deaths, and the most common type is lung adenocarcinoma (LUAD). LUAD is frequently diagnosed in people who never smoked, patients are always diagnosed at advanced inoperable stages, and the prognosis is ultimately poor. Thus, there is an urgent need for the development of novel targeted therapeutics to suppress LUAD progression. In this study, we demonstrated that the expression of DNA replication and sister chromatid cohesion 1 (DSCC1) was higher in LUAD samples than normal tissues, and the overexpression of DSCC1 or its coexpressed genes were highly correlated with poor outcomes of LUAD patients, highlighting DSCC1 might be involved in LUAD progression. Furthermore, the expression of DSCC1 was positively correlated with multiple genetic mutations which drive cancer development, including TP53, TTN, CSMD, and etc. More importantly, DSCC1 could promote the cell proliferation, stemness, EMT, and metastatic potential of LUAD cells. In addition, DSCC1 interacted with HSP90AB1 and promoted the progression of LUAD via regulating ER stress. Meanwhile, DSCC1 expression negatively correlated with immune cell infiltration in lung cancer, and DSCC1 positively regulated the expression of PD-L1 in LUAD cells. Collectively, this study revealed that DSCC1 is a novel therapeutic target to treat LUAD and a biomarker for predicting the efficiency of PD-1/PD-L1 blockade treatment.

【 授权许可】

CC BY   
© BioMed Central Ltd., part of Springer Nature 2023

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