Caprin-1 influences autophagy-induced tumor growth and immune modulation in pancreatic cancer

• Published in: Journal of translational medicine 2023-12, Vol.21 (1), p.903-16, Article 903
• Main Authors: Yang, Wenbo, Chen, Hongze, Li, Guanqun, Zhang, Tao, Sui, Yuhang, Liu, Liwei, Hu, Jisheng, Wang, Gang, Chen, Hua, Wang, Yongwei, Li, Xina, Tan, Hongtao, Kong, Rui, Sun, Bei, Li, Le
• Format: Article
• Language: English
• Subjects: Adenocarcinoma; Autophagy; Cancer therapies; Caprin-1; Care and treatment; CD4 antigen; CD8 antigen; Cell cycle; Cell death; Cellular proteins; Chemotherapy; Cytotoxicity; Data analysis; Diagnosis; Gene expression; Genetic aspects; Genomics; Health aspects; Immune activation; Immunomodulation; Immunosurveillance; Immunotherapy; Inflammation; Lymphocytes; Lymphocytes T; Macrophages; Medical prognosis; Methods; Microenvironments; Pancreatic cancer; Pancreatic ductal adenocarcinoma; Patients; Phenotypes; Phosphorylation; Prognosis; Proteins; RNA sequencing; Software; STK38; Sutures; Therapeutic targets; Transcriptomes; Tumorigenesis; Tumors; ULK1
• ISSN: 1479-5876; 1479-5876
• DOI: 10.1186/s12967-023-04693-4

Pancreatic ductal adenocarcinoma (PDAC) is characterized by rapid progression and poor prognosis. Understanding the genetic mechanisms that affect cancer properties and reprogram tumor immune microenvironment will develop new strategies to maximize the benefits for cancer therapies. Gene signatures and biological processes associated with advanced cancer and unfavorable outcome were profiled using bulk RNA sequencing and spatial transcriptome sequencing, Caprin-1 was identified as an oncogenesis to expedite pancreatic cancer growth by activating autophagy. The mechanism of Caprin-1 inducing autophagy activation was further explored in vitro and in vivo. In addition, higher level of Caprin-1 was found to manipulate immune responses and inflammatory-related pathways. The immune profiles associated with increased levels of Caprin-1 were identified in human PDAC samples. The roles of CD4 T cells, CD8 T cells and tumor associated macrophages (TAMs) on clinical outcomes prediction were investigated. Caprin-1 was significantly upregulated in advanced PDAC and correlated with poor prognosis. Caprin-1 interacted with both ULK1 and STK38, and manipulated ULK1 phosphorylation which activated autophagy and exerted pro-tumorigenic phenotypes. Additionally, the infiltrated CD4 T cells and tumor associated macrophages (TAMs) were increased in Caprin-1 tissues. The extensive CD4 T cells determined poor clinical outcome in Caprin-1 patients, arguing that highly expressed Caprin-1 may assist cancer cells to escape from immune surveillance. Our findings establish causal links between the upregulated expression of Caprin-1 and autophagy activation, which may manipulate immune responses in PDAC development. Our study provides insights into considering Caprin-1 as potential therapeutic target for PDAC treatment.