2. Academic Validation
  3. KIAA1324 Suppresses Gastric Cancer Progression by Inhibiting the Oncoprotein GRP78

KIAA1324 Suppresses Gastric Cancer Progression by Inhibiting the Oncoprotein GRP78

  • Cancer Res. 2015 Aug 1;75(15):3087-97. doi: 10.1158/0008-5472.CAN-14-3751.
Jin Muk Kang 1,  Sujin Park 1,  Staci Jakyong Kim 2,  Hyojung Kim 1,  Bona Lee 3,  Junil Kim 1,  Jinah Park 4,  Shin Tae Kim 5,  Han-Kwang Yang 6,  Woo Ho Kim 7,  Seong-Jin Kim 8
Affiliations

Affiliations

  • 1 CHA Cancer Institute, College of Life Science, CHA University, Seongnam City, Republic of Korea.
  • 2 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.
  • 3 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.
  • 4 CHA Cancer Institute, College of Life Science, CHA University, Seongnam City, Republic of Korea. College of Pharmacy, CHA University, Seongnam City, Republic of Korea.
  • 5 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.
  • 6 Cancer Research Institute, Seoul National University, Seoul, Republic of Korea. Department of Surgery, Seoul National University College of Medicine, Seoul, Republic of Korea.
  • 7 Cancer Research Institute, Seoul National University, Seoul, Republic of Korea. Department of Pathology, Seoul National University College of Medicine, Seoul, Republic of Korea.
  • 8 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.
PMID: 26045166 DOI: 10.1158/0008-5472.CAN-14-3751
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.

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