Dedicator of cytokinesis (DOCK) is a family of proteins with 11 members in mammal which can regulate cell motility, phagocytosis, myoblast fusion, tumor suppression, neuronal polarization and adhesion. They are classified into four subfamilies A to D. Dock1 (Dock180), the founding member of the family, is a large protein which includes an N-terminal SH3 domain and a flanking helical bundle that are vital to the formation of a functioning complex Dock1-ELMO1 (Gumienny et al.,2001; Grimsley et al.,2004; Komander et al., 2008). Genetic and biochemical studies show that DOCK1 acts as a guanine-nucleotide exchange factor (GEF) for the small GTPase Rac1 (Diyokawa et al., 1998; Nolan et al., 1998). Rac1 is a small GTPase required for myoblast fusion in organisms such as fruit flies, zebrafish and mice (Rochlin et al., 1998). In addition to playing an important role in a broad spectrum of biological processes, numerous studies have demonstrated contributions of DOCK members to the development of cancer. Deciphering the detailed mechanisms by which DOCK proteins participate in tumorigenesis will shed light on the design of new treatment strategies.