title: KIAA1324 Suppresses Gastric Cancer Progression by Inhibiting the Oncoprotein GRP78.
abstract: Recent advances in genome and transcriptome analysis have contributed to the identification of many potential cancer-related genes. Furthermore, biological and clinical investigations of the candidate genes provide us with a better understanding of carcinogenesis and development of cancer treatment. Here, we report a novel role of KIAA1324 as a tumor suppressor in gastric cancer. We observed that KIAA1324 was downregulated in most gastric cancers from transcriptome sequencing data and found that histone deacetylase was involved in the suppression of KIAA1324. Low KIAA1324 levels were associated with poor prognosis in gastric cancer patients. In the xenograft model, KIAA1324 significantly reduced tumor formation of gastric cancer cells and decreased development of preformed tumors. KIAA1324 also suppressed proliferation, invasion, and drug resistance and induced apoptosis in gastric cancer cells. Through protein interaction analysis, we identified GRP78 (glucose-regulated protein 78 kDa) as a KIAA1324-binding partner. KIAA1324 blocked oncogenic activities of GRP78 by inhibiting GRP78-caspase-7 interaction and suppressing GRP78-mediated AKT activation, thereby inducing apoptosis. In conclusion, our study reveals a tumor suppressive role of KIAA1324 via inhibition of GRP78 oncoprotein activities and provides new insight into the diagnosis and treatment of gastric cancer.
authors.affiliation: CHA Cancer Institute, College of Life Science, CHA University, Seongnam City, Republic of Korea.
authors.forename: Jin Muk
authors.initials: JM
authors.lastname: Kang
authors.affiliation: CHA Cancer Institute, College of Life Science, CHA University, Seongnam City, Republic of Korea.
authors.forename: Sujin
authors.initials: S
authors.lastname: Park
authors.affiliation: CHA Cancer Institute, College of Life Science, CHA University, Seongnam City, Republic of Korea. International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, Tsukuba, Japan. School of Integrative and Global Majors, University of Tsukuba, Tsukuba, Japan.
authors.forename: Staci Jakyong
authors.initials: SJ
authors.lastname: Kim
authors.affiliation: CHA Cancer Institute, College of Life Science, CHA University, Seongnam City, Republic of Korea.
authors.forename: Hyojung
authors.initials: H
authors.lastname: Kim
authors.affiliation: CHA Cancer Institute, College of Life Science, CHA University, Seongnam City, Republic of Korea. College of Pharmacy, Sookmyung Women's University, Seoul, Republic of Korea.
authors.forename: Bona
authors.initials: B
authors.lastname: Lee
authors.affiliation: CHA Cancer Institute, College of Life Science, CHA University, Seongnam City, Republic of Korea.
authors.forename: Junil
authors.initials: J
authors.lastname: Kim
authors.affiliation: CHA Cancer Institute, College of Life Science, CHA University, Seongnam City, Republic of Korea. College of Pharmacy, CHA University, Seongnam City, Republic of Korea.
authors.forename: Jinah
authors.initials: J
authors.lastname: Park
authors.affiliation: CHA Cancer Institute, College of Life Science, CHA University, Seongnam City, Republic of Korea. Division of Pulmonary Medicine, Department of Internal Medicine, CHA Gangnam Medical Center, College of Medicine, CHA University, Republic of Korea.
authors.forename: Shin Tae
authors.initials: ST
authors.lastname: Kim
authors.affiliation: Cancer Research Institute, Seoul National University, Seoul, Republic of Korea. Department of Surgery, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Han-Kwang
authors.initials: HK
authors.lastname: Yang
authors.affiliation: Cancer Research Institute, Seoul National University, Seoul, Republic of Korea. Department of Pathology, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Woo Ho
authors.initials: WH
authors.lastname: Kim
authors.affiliation: CHA Cancer Institute, College of Life Science, CHA University, Seongnam City, Republic of Korea. Department of Biomedical Science, College of Life Science, CHA University, Seongnam City, Republic of Korea. kimsj@cha.ac.kr.
authors.forename: Seong-Jin
authors.initials: SJ
authors.lastname: Kim
mesh_terms: D000368:Aged; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D000091342:Endoplasmic Reticulum Chaperone BiP; D015972:Gene Expression Regulation, Neoplastic; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008565:Membrane Proteins; D051379:Mice; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D013274:Stomach Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D023041:Xenograft Model Antitumor Assays
chemical_list: C491832:ELAPOR1 protein, human; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; C000717248:Hspa5 protein, mouse; D008565:Membrane Proteins; D009363:Neoplasm Proteins