1. Medical Oncology, CHA Bundang Medical Center, CHA University, Seongnam, Korea;
2. Laboratory of Tumor Vasculature and Microenvironment, CHA University, Seongnam, Korea;
3. Asan Institute for Life Sciences, Seoul, Korea;
4. Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Korea;
5. Division of Medical Oncology, Yonsei University College of Medicine, Seoul, Korea;
6. Song-Dang Institute for Cancer Research;
7. Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea.
Rho GTPases play a pivotal role in tumor progression by regulating tumor cell migration and invasion. However, the role of Rho GTPases in gastric cancer (GC) remains unexplored. This study aimed to investigate the clinical implications of RhoJ, which is an uncharted member of Rho family. RhoJ expression in human GC cell lines and surgical specimens from GC patients were analyzed. Moreover, in vitro gain-of-function analysis was performed to evaluate the malignant phenotypes of RhoJ-overexpressing GC cells. The extent of RhoJ expression varied among GC cell lines and GC patients. YCC-9 cell line displayed the strongest expression, while YCC-10, -11, and -16 showed scant expressions. Of the 70 GC patients, 34 (48.6%) had RhoJ expression in their GC tissue, and patients with high RhoJ expression had more diffuse type GC (73.5% vs. 41.7%), were at more advanced stages (stage III, IV: 85.3% vs. 58.4%), and had more frequent metastasis (47.1% vs. 11.1%), denoting that RhoJ has a potential role in GC progression and metastasis. High RhoJ expression significantly correlated with poor overall survival and recurrence-free survival after surgical resection of gastric cancer. Finally, In vitro gain-of-function experiments showed 41.3% enhanced motility and 60.4% enhanced invasiveness in RhoJ-overexpressing GC cells compared to control, with negligible difference in cell proliferation. Collectively, high RhoJ expression is an independent negative prognostic factor for the survival outcome of GC and correlated with the increased cell motility and invasiveness.
Keywords: RhoJ, Rho GTPase, gastric cancer, progression, metastasis.