REG3A secreted by peritumoral acinar cells enhances pancreatic ductal adenocarcinoma progression via activation of EGFR signaling
文献类型：期刊论文
| 作者 | Ren, Xiaojing8; Teng, Yunfei7; Xie, Kunxin6; He, Xiao5,7; Chen, Gang5,7; Zhang, Kaini4; Liao, Qingyi3; Zhang, Jia6; Zhou, Xiaohang6; Zhu, Yating6 |
| 刊名 | CELL COMMUNICATION AND SIGNALING
 |
| 出版日期 | 2025-02-18 |
| 卷号 | 23期号:1页码:19 |
| 关键词 | REG3A Pancreatic ductal adenocarcinoma Peritumoral acinar cell Epidermal growth factor receptor (EGFR) Paracrine |
| DOI | 10.1186/s12964-025-02103-4 |
| 英文摘要 | BackgroundRegenerating family member 3A (REG3A) is involved in the development of multiple malignant tumors, including pancreatic ductal adenocarcinoma (PDAC). However, any role of REG3A in PDAC remains controversial due to its unclear tissue localization or direct receptors, and complex downstream signal transductions.MethodsMorphological analysis and public multi-omics data retrieval were was utilized to elucidate the tissue localization of REG3A in PDAC. To ascertain the pro-oncogenic role of secreted REG3A, experiments were conducted using in vitro PDAC cell lines and in vivo tumor formation assays in nude mice. A battery of investigative techniques, including RNA sequencing, phospho-kinase arrays, western blot analyses, in silico docking simulations, gene truncation strategies, and co-immunoprecipitation, were employed to delve into the downstream signaling transduction pathways induced by REG3A.ResultsIn this study, we confirmed an association between increased serum levels of REG3A and poor prognosis in patients with PDAC. Morphological staining and bioinformatic analysis showed that REG3A was mainly expressed in peritumoral acinar cells that were spatially close to tumor region, while it was almost negative in PDAC tumor cells. Peritumoral REG3A expression levels, but not tumoral REG3A, were highly correlated with PDAC progression. Further in vitro experiments including RNA sequencing and molecular biological assays revealed that secreted REG3A could directly bind to the epidermal growth factor receptor (EGFR), an important pro-oncogene involved in cellular proliferation, and subsequently activate the downstream mitogen-activated protein kinase (MAPK) signals to promote PDAC tumor cell growth.ConclusionTaken together, our data indicated that increased expression of REG3A in peritumoral acinar cells acts as a specific event to indicate PDAC progression, and verified EGFR as a possible target of REG3A, providing mechanistic insights into the role of REG3A, the diagnostic method and therapeutic strategy of PDAC. |
| WOS关键词 | BETA-CELLS ; CANCER ; OVEREXPRESSION ; PROTECTS ; GROWTH ; PROLIFERATION ; NETWORK ; PATHWAY ; SERVER |
| 资助项目 | National Natural Science Foundation of China[82172991] ; National Natural Science Foundation of China[81502089] ; National Natural Science Foundation of China[81603169] ; National Natural Science Foundation of China[81570779] ; National Natural Science Foundation of China[81170252] ; National Natural Science Foundation of China[81070656] ; National Natural Science Foundation of China[81670619] ; National Natural Science Foundation of China[81870467] ; National Natural Science Foundation of China[82302922] ; Natural Science Research Program for Higher Education in Jiangsu Province[21KJB320015] ; National Key Research and Development Program of China[2022YFF0713005] |
| WOS研究方向 | Cell Biology |
| 语种 | 英语 |
| WOS记录号 | WOS:001425507500003 |
| 出版者 | BMC |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/316269]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Su, Dongming; Sun, Peng; Ding, Ying |
| 作者单位 | 1.Kobe Univ, Grad Sch Hlth Sci, Dept Rehabil Sci, 7-10-2 Tomogaoka, Kobe, Hyogo 6540142, Japan 2.Nanjing Med Univ, Affiliated Canc Hosp, Jiangsu Inst Canc Res, Dept Pathol,Jiangsu Canc Hosp, Nanjing 210009, Peoples R China 3.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China 4.Nanjing Med Univ, Dept Pathophysiol, Nanjing 211166, Peoples R China 5.Nanjing Med Univ, Affiliated Hosp 1, Dept Pathol, Nanjing 210029, Peoples R China 6.Nanjing Med Univ, Dept Biochem & Mol Biol, Key Lab Human Funct Genom Jiangsu Prov, Nanjing 211166, Peoples R China 7.Nanjing Med Univ, Dept Pathol, Nanjing 211166, Peoples R China 8.Shanxi Med Univ, Shanxi Bethune Hosp, Tongji Shanxi Hosp, Shanxi Acad Med Sci,Hosp 3, Taiyuan 030032, Peoples R China |
| 推荐引用方式 GB/T 7714 | Ren, Xiaojing,Teng, Yunfei,Xie, Kunxin,et al. REG3A secreted by peritumoral acinar cells enhances pancreatic ductal adenocarcinoma progression via activation of EGFR signaling[J]. CELL COMMUNICATION AND SIGNALING,2025,23(1):19. |
| APA | Ren, Xiaojing.,Teng, Yunfei.,Xie, Kunxin.,He, Xiao.,Chen, Gang.,...&Ding, Ying.(2025).REG3A secreted by peritumoral acinar cells enhances pancreatic ductal adenocarcinoma progression via activation of EGFR signaling.CELL COMMUNICATION AND SIGNALING,23(1),19. |
| MLA | Ren, Xiaojing,et al."REG3A secreted by peritumoral acinar cells enhances pancreatic ductal adenocarcinoma progression via activation of EGFR signaling".CELL COMMUNICATION AND SIGNALING 23.1(2025):19. |
入库方式： OAI收割
来源：上海药物研究所
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