title: GRP78 secreted by colon cancer cells facilitates cell proliferation via PI3K/Akt signaling.
abstract: Glucose regulated protein 78 (GRP78) is usually recognized as a chaperone in the endoplasmic reticulum. However, increasing evidence indicates that GRP78 can be translocated to the cell surface, acting as a signaling receptor for a variety of ligands. Since little is known about the secretion of GRP78 and its role in the progression of colon cancer we here focused on GRP78 from colon cancer cells, and purified GRP78 protein mimicking the secreted GRP78 was able to utilize cell surface GRP78 as its receptor, activating downstream PI3K/Akt and Wnt/β-catenin signaling and promote colon cancer cell proliferation. Our study revealed a new mode of action of autocrine GRP78 in cancer progression: secreted GRP78 binds to cell surface GRP78 as its receptor and activates intracellular proliferation signaling.
authors.affiliation: Institute of Biotechnology, Key Laboratory of Chemical Biology and Molecular Engineering of National Ministry of Education, Shaxi University, Taiyuan, China E-mail : lzy@sxu.edu.cn.
authors.forename: Rong
authors.initials: R
authors.lastname: Fu
authors.forename: Peng
authors.initials: P
authors.lastname: Yang
authors.forename: Hai-Li
authors.initials: HL
authors.lastname: Wu
authors.forename: Zong-Wei
authors.initials: ZW
authors.lastname: Li
authors.forename: Zhuo-Yu
authors.initials: ZY
authors.lastname: Li
mesh_terms: D049109:Cell Proliferation / Q000502:physiology*; D003110:Colonic Neoplasms / Q000378:metabolism*; D000091342:Endoplasmic Reticulum Chaperone BiP; D019073:HT29 Cells; D006360:Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction; D060449:Wnt Signaling Pathway
chemical_list: D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; C000717247:HSPA5 protein, human