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CMIP promotes Herceptin resistance of HER2 positive gastric cancer cells
Affiliation:1. School of Nursing, Anhui Medical University, Hefei, Anhui, 230032, China;2. Department of Pathology, School of Basic Medicine, Anhui Medical University, Hefei, Anhui, 230032, China;1. Department of Pathology, The First People''s Hospital of Fuyang, Hangzhou, 311400, PR China;2. Department of Pathology, Key Laboratory of Disease Proteomics of Zhejiang Province, School of Medicine, Zhejiang University, Hangzhou, 310058, China;3. Department of Toxicology, School of Public Health, Zhejiang University, Hangzhou, 310058, China;1. Department of Urology, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China;2. Department of Urology, The Affiliated Hospital of Jiangsu University, Zhenjiang, 212001, Jiangsu, China;1. Paris-Diderot University, Sorbonne Paris Cite, Lariboisiere Hospital, INSERM U965, Paris, France;2. Service of Visceral and Vascular Radiology, APHP, Lariboisiere Hospital, Paris-Diderot University, Sorbonne Paris Cite, AP-HP, Paris, France;3. Paris-Diderot University, Sorbonne Paris Cite, AP-HP, Beaujon Hospital, INSERM U728, Clichy, France;4. Service of Digestive and Cancer Surgery, APHP, Lariboisiere Hospital, Paris-Diderot University, Sorbonne Paris Cite, AP-HP, Paris, France;5. Service of Clinical Physiology— Functional Investigations, APHP, Lariboisiere Hospital, Paris-Diderot University, Sorbonne Paris Cite, AP-HP, Paris, France;1. Department of Pathology, Eulji University Hospital, Eulji University School of Medicine, Daejeon, Republic of Korea;2. Eulji University School of Medicine, Daejeon 34824, Republic of Korea;3. Department of Forensic Medicine, National Forensic Service Busan Institute, Yangsan, Republic of Korea;4. Department of Internal Medicine, Eulji University Hospital, Eulji University School of Medicine, Daejeon, Republic of Korea
Abstract:Gastric cancer remains one of the most malignant human cancers with poor prognosis. Herceptin is a well-received antibody drug for HER2 positive gastric cancer. Primary Herceptin resistance and acquired Herceptin resistance retarded the use of Herceptin for gastric cancer. We herein reported CMIP (C-Maf-inducing protein) was overexpressed in Herceptin-resistant gastric cancer cells MKN45-HR and NCI-N87-HR; CMIP promoted Herceptin resistance of HER2 positive gastric cancer cells. SOX2 was examined to be positively regulated by CMIP and also promoted Herceptin resistance of HER2 positive gastric cancer cells. SOX2 might mediate the Herceptin resistance promoting role of CMIP in gastric cancer cells. Elevated expression of CMIP was associated with poor clinicopathological features including tumor size, lymph node metastasis and clinical stage in HER2 positive gastric cancer patients. Inhibitors of CMIP could be used as potential adjuvant therapeutic drugs for HER2 positive gastric cancer.
Keywords:CMIP  SOX2  Herceptin resistance  Gastric cancer
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