RhoGDI2 expression is associated with tumor growth and malignant progression of gastric cancer.
OBJECTIVE
Rho GDP dissociation inhibitor 2 (RhoGDI2) has been identified as a regulator of Rho family GTPase. However, there is currently no direct evidence suggesting whether RhoGDI2 activates or inhibits Rho family GTPase in vivo (and which type), and the role of RhoGDI2 in tumor remains controversial. Here, we assessed the effects of RhoGDI2 expression on gastric tumor growth and metastasis progression.


METHODS
Proteomic analysis was done to investigate the tumor-specific protein expression in gastric cancer and RhoGDI2 was selected for further study. Immunohistochemistry was used to detect RhoGDI2 expression in clinical samples of primary gastric tumor tissues which have different pathologic stages. Gain-of-function and loss-of-function approaches were done to examine the malignant phenotypes of the RhoGDI2-expressing or RhoGDI2-depleting cells.


RESULTS
RhoGDI2 expression was correlated positively with tumor progression and metastasis potential in human gastric tumor tissues, as well as cell lines. The forced expression of RhoGDI2 caused a significant increase in gastric cancer cell invasion in vitro, and tumor growth, angiogenesis, and metastasis in vivo, whereas RhoGDI2 depletion evidenced opposite effects.


CONCLUSIONS
Our findings indicate that RhoGDI2 is involved in gastric tumor growth and metastasis, and that RhoGDI2 may be a useful marker for tumor progression of human gastric cancer.
Department of Microbiology/Research Institute of Life Science, College of Natural Sciences, Physiology, Anatomy and Neurobiology, Institute of Health Science, Gyeongsang National University, Jinju, Korea.
Hee Jun
HJ
Cho
Kyoung Eun
KE
Baek
Sun-Mi
SM
Park
In-Kyu
IK
Kim
Yeong-Lim
YL
Choi
Hye-Jung
HJ
Cho
In-Koo
IK
Nam
Eun Mi
EM
Hwang
Jae-Yong
JY
Park
Jae Yoon
JY
Han
Sang Soo
SS
Kang
Dong Chul
DC
Kim
Won Sup
WS
Lee
Mi-Ni
MN
Lee
Goo Taeg
GT
Oh
Jae Won
JW
Kim
Chang Won
CW
Lee
Jiyun
J
Yoo
D000818:Animals; D045744:Cell Line, Tumor; D018450:Disease Progression; D055785:Gene Knockdown Techniques; D020730:Guanine Nucleotide Dissociation Inhibitors / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D040901:Proteomics; D034741:RNA, Small Interfering / Q000378:metabolism; D013274:Stomach Neoplasms / Q000378:metabolism / Q000473:pathology*; D014183:Transplantation, Heterologous; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis* / Q000235:genetics; D062949:rho Guanine Nucleotide Dissociation Inhibitor beta; D062947:rho-Specific Guanine Nucleotide Dissociation Inhibitors
C569658:ARHGDIB protein, human; D020730:Guanine Nucleotide Dissociation Inhibitors; D034741:RNA, Small Interfering; D025521:Tumor Suppressor Proteins; D062949:rho Guanine Nucleotide Dissociation Inhibitor beta; D062947:rho-Specific Guanine Nucleotide Dissociation Inhibitors