. Author manuscript; available in PMC: 2017 Jun 19.

Published in final edited form as: Oncogene. 2016 Dec 19;36(23):3213–3222. doi: 10.1038/onc.2016.473

Table 1.

Function of Rho GTPases in in vivo cancer models.

Rho GTPases	Pro- or anti- oncogenic	Model	Remarks	References (year)
RhoC	Pro-oncogenic	RhoC^−/−; pyV-MT mouse model of mammary tumor	Loss of RhoC did not affect tumor development but decreases tumor cell motility and metastatic cell survival leading to a drastic inhibition of metastasis	Hakem et al.⁴⁷ (2005)
Rac1	Pro-oncogenic	Rac1^flox/flox and LSL-K-Ras^G12D mouse, lung infections with adenovirus expressing Cre (Ad-Cre)	Rac1 function is required for tumorigenesis in this oncogenic K-Ras-induced lung cancer model	Kissil et al.⁵⁰ (2007)
Rac1	Pro-oncogenic	Rac1^flox/flox; K5-Cre mouse, treated with DMBA/TPA to induce skin tumors	Rac1 is crucial for skin tumor formation and mice with keratinocyte-restricted deletion of Rac1 are resistant to skin tumor formation.	Wang et al.⁵² (2010)
Rac1	Pro-oncogenic	LSL-K-Ras^G12D; K14-Cre:ER; Rac1^WT/− mouse model of epidermal papilloma	Active Rac1 level was high in this model and genetic removal of one Rac1 allele significantly impaired K- Ras induced oral papilloma growth	Samuel et al.⁵¹ (2011)
Rac1/Rac2	Pro-oncogenic	Transplant of Low density bone marrow from Rac1^flox/flox; Mx1-Cre or Rac2^−/−; Mx1- Cre mouse, transfected with retrovirus expressing MLL-AF9 to induce leukemia.	Rac2, but not Rac1, is critical to the initiation of acute myeloid leukemia in this model; however, loss of either Rac1 or Rac2 is sufficient to impair survival and growth of the transformed MLL-AF9 leukemia	Mizukawa et al.⁵⁴ (2011)
RhoA/Rac1	Pro-oncogenic	Oncogenic Ras driven eye hyperplasia /tumorigenesis in Drosophila (ey-GAL4; UAS-Ras85D^V12)	Rho1, Rac1 and RhoGEF2 were identified to enhance oncogenic Ras driven tumorigenesis in a genome-wide screen	Brumby et al.³¹ (2011)
RhoA	Pro-oncogenic	K-Ras^LA2-G12D mouse model of non-small cell lung cancer (NSCLC)	Combined inhibition of the proteasome and ROCK robustly suppresses K-Ras mutant tumor growth	Kumar et al.³² (2012)
Rac1b	Pro-oncogenic	LSL-K-Ras^G12D; Rosa26-LSL-Rac1b mouse model of lung cancer, lung infection with adenovirus expressing Cre (Ad-Cre)	Expression of Rac1b synergized with oncogenic K- Ras resulting in increased cellular proliferation and accelerated tumor growth.	Zhou et al.⁶⁴ (2013)
Rac1	Pro-oncogenic	Rac1^flox/flox; K-Ras^(LSL-G12D)/+; Ptf1a^cre/+ mouse model of pancreatic ductal adenocarcinoma (PDA) with pancreas- specific deletion of Rac1	Pancreas-specific deletion of Rac1 prevented the development of pancreatic tumors.	Wu et al.⁵³ (2014)
Cdc42	Pro-oncogenic	APC^min/+; Cdc42^flox/flox; Vil-Cre or Catnb^(ex3)/+; Cdc42^flox/flox; Vil-Cre mouse model of colorectal cancer with intestinal epithelial cell specific Cdc42 deletion	Reduction of Cdc42 alleviates the tumorigenicity of mutant intestinal cells carrying single APC or β- catenin mutations	Sakamori et al.⁵⁸ (2014)
RhoA	Anti-oncogenic	TO(K-Ras^G12V/RhoA), TO(K- Ras^G12V/RhoA^T19N), or TO(K- Ras^G12V/RhoA^G14V) zebra fish model of hepatocellular carcinoma	Liver enlargement and hepatocyte proliferation induced by tet-on-inducible, liver-specific expression K-Ras^G12V was augmented by dominant- negative RhoA^T19N, but reduced by constitutive- active RhoA^G14V.	Chew et al.⁹⁴ (2014)
RhoA	Anti-oncogenic	APC^min/+; RhoAT^19N/−; Vil-Cre^tg/− mouse model of colorectal cancer with expression of dominant-negative RhoA^T19N	RhoA inactivation contributes to colorectal cancer progression/metastasis, largely through the activation of Wnt/β-catenin signaling	Rodrigues et al.⁹⁷ (2014)
RhoB	Anti-oncogenic	RhoB^−/− mouse with cutaneous squamous cell carcinomas (SCC) induced with UVB	RhoB deletion lowered the incidence of SCC precursor tumors following chronic exposure to UVB.	Meyer et al.¹¹² (2014)
Rac1	Pro-oncogenic	K14-ΔNLef1; K14-Rac1^Q61L mouse model of sebaceous adenoma with epidermis- specific active Rac1	Active Rac1 did not change the incidence or frequency of tumors, but could suppress tumor cell differentiation and enable malignant progression of sebaceous tumors.	Frances et al.⁵⁶ (2015)
RhoA/RhoC	Anti-oncogenic	LSL-K-Ras^G12D with RhoA^flox/flox or RhoC^−/− or both, mouse models of lung carcinoma induced by lung infection of adenovirus expressing Cre (Ad-Cre)	Deletion of RhoA or RhoC alone did not suppress K- RasG12D induced lung adenoma initiation; rather, deletion of RhoA along accelerated lung adenoma formation.	Zandvakili et al.⁹⁸ (2015)