# RAC1B: A Rho GTPase with Versatile Functions in Malignant Transformation and Tumor Progression
## 5 Biological Functions of RAC1B  
### Cancer Progression/Cellular Transformation  
A series of studies suggests that RAC1B contributes to cellular transformation. Rac1b, like the constitutively-activated and transforming Rac1-Q61L mutant, promoted cellular transformation, e.g., a loss of density- and anchorage-dependent growth inhibition of NIH3T3 mouse fibroblasts [7]. RAC1B overexpression may also facilitate tumor progression by interaction with certain tumor-associated signaling pathways (either functional or deregulated as a consequence of oncogene activation or tumor suppressor protein inactivation). The expression of RAC1B was found to be elevated in CRC at various stages of neoplastic progression. In this tumor type, RAC1B can enhance Dishevelled-3 (DVL3)-mediated Wnt pathway signaling and induction of Wnt target genes specifically involved in decreasing the adhesive properties of CRC cells [20]. RAC1B is also overexpressed most prominently in stages 1 and 2 of human lung adenocarcinomas [23]. In a mouse model of this cancer type, in which the expression of Rac1b can be conditionally activated in the lung, expression of Rac1b alone was insufficient to initiate lung tumor formation but cooperation with oncogenic K-Ras resulted in enhanced proliferation and accelerated tumor growth [24]. Other potential protumorigenic mechanisms include the ability of RAC1B to counteract oncogene (B-RAF-V600E)-induced senescence (OIS) in CRC cells, indicating the selection for increased RAC1B expression as a potential mechanism by which these cells can escape from OIS (see Section 5.8). In addition, MMP-induced expression of Rac1b gave rise to lung adenocarcinoma in transgenic mice through bypassing OIS [23]. Very recently, it was reported that ARHGAP11A facilitates malignant progression in HCC patients via ARHGAP11A-RAC1B interaction [22].  
[PERSON] and coworkers induced ectopic expression of Rac1b in mouse intestinal epithelial cells after crossing Rosa26-LSL-Rac1b and villin-Cre mice [25]. These animals were bred with ApcMin/+ or IL10\({}^{-/-}\) mice to trigger intestinal tumors. Rac1b ectopic expression increased intestinal epithelial cell proliferation and migration and enhanced the production of ROS. Although Rac1b overexpression alone was not sufficient to drive intestinal neoplasia, it enhanced Apc-dependent intestinal tumorigenesis. In IL10 knockout mice, the Rac1b transgene promoted cecum and proximal colon carcinogenesis. In contrast, when the above mice received treatment with azoxymethane (AOM)/dextran sulfate sodium (DSS), Rac1b alleviated carcinogen/acute inflammation-associated colon carcinogenesis resulting in part from the early mucosal repair after resolution of inflammation. These data highlight the critical role of Rac1b in cooperating with Wnt pathway dysregulation and chronic inflammation to promote intestinal carcinogenesis [25].  
RAC1B has protumorigenic function also in thyroid carcinoma. NF\(\kappa\)B activation has been implicated as one of the molecular mechanisms associated with the protumorigenic advantage of RAC1B overexpression in thyroid carcinomas [26]. Figure 1 provides a summary on the protumorigenic mechanisms discussed above.