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Perturbations, such as hypoxia, oxidative stress, inadequate amino acid supply, Ca\n                      <jats:sup>2+<\/jats:sup>\n                      imbalance, and acidosis, can disrupt cellular equilibrium and result in the accumulation of misfolded\/unfolded proteins within the ER lumen. This triggers ER stress. In response to this stress, an unfolded protein response (UPR) is activated as a mechanism to cope with the stress and restore internal balance. The UPR is regulated by three sensors located in the ER: inositol\u2010requiring enzyme 1 (IRE1), protein kinase RNA\u2010like endoplasmic reticulum kinase (PERK), and activating transcription factor 6 (ATF6). However, the UPR can promote tumor growth in\u00a0vivo by affecting tumor angiogenesis, cell migration, cell metabolism, and treatment resistance, and has a huge impact on the tumor microenvironment.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>We conducted a literature review of scientific papers on the topic of ER stress in the tumor microenvironment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results and Discussion<\/jats:title>\n                    <jats:p>This review focuses on the inducing factors of ER stress, the mechanism of the UPR signaling pathway induced by ER stress, and the effect of ER stress on the tumor microenvironment and immune\u2010infiltrating cells. Tumors can regulate their evolution by affecting themselves and the tumor microenvironment through endoplasmic reticulum stress. This study reveals the important role of endoplasmic reticulum stress in the occurrence and development of tumors, and provides new ideas and potential therapeutic targets for the precision treatment of tumors. Future studies can further explore the molecular mechanism of ER stress regulating tumor microenvironment and explore its application potential in clinical diagnosis and treatment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cam4.70684","type":"journal-article","created":{"date-parts":[[2025,3,11]],"date-time":"2025-03-11T18:37:38Z","timestamp":1741718258000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Endoplasmic Reticulum Stress: Triggers Microenvironmental Regulation and Drives Tumor Evolution"],"prefix":"10.1002","volume":"14","author":[{"given":"Chaosheng","family":"Peng","sequence":"first","affiliation":[{"name":"Department of Digestive Surgery Xijing Hospital of Digestive Diseases, Fourth Military Medical University  Xi'an China"},{"name":"State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive Diseases Xijing 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