MerTK is a novel therapeutic target in gastric cancer
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Jun Ho Yi1,5,*, Jiryeon Jang1,*, Jeonghee Cho2,*, In-Gu Do3, Mineui Hong4, Seung Tae Kim1, Kyoung-Mee Kim4, Sujin Lee1, Se Hoon Park1, Joon Oh Park1,4, Young Suk Park1, Won Ki Kang1, Ho Yeong Lim1 and Jeeyun Lee1
1Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
2Samsung Genome Institute, Seoul, Korea
3Department of Pathology, Kangbuk Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
4Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
5Division of Hematology-Oncology, Department of Medicine, Hanyang University Hospital, Seoul, Korea
*These authors have contributed equally to this work
Ho Yeong Lim, e-mail: firstname.lastname@example.org
Jeeyun Lee, e-mail: email@example.com
Keywords: gastric cancer, MerTK, patient-derived cells
Received: February 28, 2014 Accepted: April 08, 2015 Published: April 20, 2015
Introduction: The role of MerTK has not been assessed in gastric cancer (GC). The aim of this study was to identify a subgroup of GC patients with MerTK tumor overexpression, and to evaluate MerTK as a potential therapeutic target in this disease.
Methods: Protein and mRNA expression of MerTK were evaluated, and other various in vitro analyses including shRNA transfection, cell cycle anslysis, MTS assay and colony forming assay were carried out with GC cell lines and GC patient-derived cells (PDCs).
Results: shRNA-mediated knockdown of MerTK resulted in inhibition of cell growth, as well as increased cellular apoptosis in MerTK positive GC cells. Out of 192 GC patients, 16 (8.3%) patients showed strong protein expression and they had a significantly shorter overall survival compared to those with no MerTK expression. In 54 cases of GC PDCs, 4 cases (7.4%) showed mRNA overexpression, which was comparable to the protein expression rate. When we administered UNC1062, a novel MerTK-selective small molecular tyrosine kinase inhibitor, proliferation of MerTK overexpressing GC cells and PDCs were considerably inhibited.
Conclusion: MerTK may be involved in GC carcinogenesis, and it could be a potential novel therapeutic target in GC patients.
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