title: Glucose-regulated protein 78 contributes to the proliferation and tumorigenesis of human colorectal carcinoma via AKT and ERK pathways.
abstract: Glucose-regulated protein 78 (GRP78), a molecular chaperon in the endoplasmic reticulum (ER), is overexpressed in a variety of tumor types and plays a critical role in cancer cell proliferation, migration, invasion and drug resistance. However, the mechanisms underlying the role of GRP78 in tumor carcinogenesis remain largely unknown. In the present study, we found that GRP78 knockdown in colorectal carcinoma (CRC) cells significantly inhibited cell proliferation, colony formation and tumorigenesis in vitro and in vivo. The proliferation inhibition of CRC cells by GRP78 knockdown was associated with an S phase arrest, a reduced G1/S transition, and a downregulation of phosphorylation of AKT and ERK1/2, key cell cycle regulatory proteins. In addition, GRP78 knockdown enhanced the apoptosis induced by 5-fluorouracil (5-FU) in CRC cells. Taken together, our results indicate that GRP78 plays an important role in the development and progression of CRC and may have therapeutic potential for CRC patients.
authors.affiliation: Department of Pathology, Affiliated Hospital of Qingdao University, Qingdao, Shandong 266000, P.R. China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Department of Pathology, Affiliated Hospital of Qingdao University, Qingdao, Shandong 266000, P.R. China.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Xing
authors.affiliation: Department of Obstetrics, Qingdao Municipal Hospital, Qingdao, Shandong 266000, P.R. China.
authors.forename: Shuping
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Affiliated Hospital of Qingdao University, Qingdao, Shandong 266000, P.R. China.
authors.forename: Lili
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Pathology, Affiliated Hospital of Qingdao University, Qingdao, Shandong 266000, P.R. China.
authors.forename: Chengqin
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Pathology, Affiliated Hospital of Qingdao University, Qingdao, Shandong 266000, P.R. China.
authors.forename: Lin
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Pathology, Affiliated Hospital of Qingdao University, Qingdao, Shandong 266000, P.R. China.
authors.forename: Qiuxia
authors.initials: Q
authors.lastname: Ji
authors.affiliation: Department of Oncology, Affiliated Hospital of Qingdao University, Qingdao, Shandong 266000, P.R. China.
authors.forename: Huamin
authors.initials: H
authors.lastname: Liu
mesh_terms: D017209:Apoptosis / Q000235:genetics; D063646:Carcinogenesis / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D004721:Endoplasmic Reticulum / Q000235:genetics; D000091342:Endoplasmic Reticulum Chaperone BiP; D005472:Fluorouracil / Q000008:administration & dosage; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D055785:Gene Knockdown Techniques; D006360:Heat-Shock Proteins / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D020935:MAP Kinase Signaling System / Q000235:genetics; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics*; D016196:S Phase / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics
chemical_list: D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; D051057:Proto-Oncogene Proteins c-akt; D005472:Fluorouracil