title: Rho GTPase RhoJ is Associated with Gastric Cancer Progression and Metastasis.
abstract: 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.
authors.affiliation: 1. Medical Oncology, CHA Bundang Medical Center, CHA University, Seongnam, Korea;; 2. Laboratory of Tumor Vasculature and Microenvironment, CHA University, Seongnam, Korea;
authors.forename: Chan
authors.initials: C
authors.lastname: Kim
authors.affiliation: 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;
authors.forename: Hannah
authors.initials: H
authors.lastname: Yang
authors.affiliation: 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;
authors.forename: Intae
authors.initials: I
authors.lastname: Park
authors.affiliation: 1. Medical Oncology, CHA Bundang Medical Center, CHA University, Seongnam, Korea;; 2. Laboratory of Tumor Vasculature and Microenvironment, CHA University, Seongnam, Korea;
authors.forename: Hong Jae
authors.initials: HJ
authors.lastname: Chon
authors.affiliation: 5. Division of Medical Oncology, Yonsei University College of Medicine, Seoul, Korea;
authors.forename: Joo Hoon
authors.initials: JH
authors.lastname: Kim
authors.affiliation: 6. Song-Dang Institute for Cancer Research;
authors.forename: Woo Sun
authors.initials: WS
authors.lastname: Kwon
authors.affiliation: 6. Song-Dang Institute for Cancer Research;
authors.forename: Won Suk
authors.initials: WS
authors.lastname: Lee
authors.affiliation: 6. Song-Dang Institute for Cancer Research;
authors.forename: Tae Soo
authors.initials: TS
authors.lastname: Kim
authors.affiliation: 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.
authors.forename: Sun Young
authors.initials: SY
authors.lastname: Rha
keywords: Rho GTPase; RhoJ; gastric cancer; metastasis.; progression