Dock6-KO Mouse

Dock6, a guanine nucleotide exchange factor (GEF) for Rac1 and CDC42, is involved in regulating the activity of RHO-GTPases, which play crucial roles in cell migration, adhesion, and cytoskeletal organization. It is associated with the WNT/β -catenin signaling pathway, a key regulator in embryonic development and tissue homeostasis [1].

Mutations in the DOCK6 gene are responsible for an autosomal-recessive variant of Adams-Oliver syndrome. This syndrome is characterized by aplasia cutis congenita, terminal transverse limb defects, along with brain and eye anomalies, and intellectual disability [2,4,5]. In cancer, elevated DOCK6 expression in gastric cancer is linked to chemo-and radioresistance, and it promotes cancer stem cell characteristics through Rac1 activation. In oral squamous cell cancer, overexpression of DOCK6 promotes cellular migration and invasion and is associated with poor prognosis [1,3].

In conclusion, Dock6 is essential for normal development as demonstrated by its role in Adams-Oliver syndrome. In cancer, it has significant implications for tumor progression, resistance to treatment, and prognosis. Studies on Dock6, especially through gene-related disease models, help in understanding its role in these biological processes and diseases, potentially leading to new therapeutic strategies.

References:

1. Chi, Hsiang-Cheng, Tsai, Chung-Ying, Wang, Chia-Siu, Chen, Wei-Jan, Lin, Kwang-Huei. 2020. DOCK6 promotes chemo- and radioresistance of gastric cancer by modulating WNT/β-catenin signaling and cancer stem cell traits. In Oncogene, 39, 5933-5949. doi:10.1038/s41388-020-01390-0. https://pubmed.ncbi.nlm.nih.gov/32753649/

2. Zepeda-Romero, Luz Consuelo, Zenker, Martin, Schanze, Denny, Corona-Rivera, Alfredo, Corona-Rivera, Jorge Román. 2022. Intrafamilial phenotypic variability in autosomal recessive DOCK6-related Adams-Oliver syndrome. In European journal of medical genetics, 65, 104653. doi:10.1016/j.ejmg.2022.104653. https://pubmed.ncbi.nlm.nih.gov/36330903/

3. Zhang, Ze-Ying, Sun, Yuan-Yuan, Wang, He-Chen, Fu, Wei-Neng, Sun, Chang-Fu. 2021. Overexpression of DOCK6 in oral squamous cell cancer promotes cellular migration and invasion and is associated with poor prognosis. In Archives of oral biology, 133, 105297. doi:10.1016/j.archoralbio.2021.105297. https://pubmed.ncbi.nlm.nih.gov/34742001/

4. Sukalo, Maja, Tilsen, Felix, Kayserili, Hülya, Southgate, Laura, Zenker, Martin. 2015. DOCK6 mutations are responsible for a distinct autosomal-recessive variant of Adams-Oliver syndrome associated with brain and eye anomalies. In Human mutation, 36, 593-8. doi:10.1002/humu.22795. https://pubmed.ncbi.nlm.nih.gov/25824905/

5. Nieto-Benito, Lula Maria, Suárez-Fernández, Ricardo, Campos-Domínguez, Minia. 2023. A novel pathogenic variation of DOCK6 gene: the genotype-phenotype correlation in Adams-Oliver syndrome. In Molecular biology reports, 50, 5519-5521. doi:10.1007/s11033-023-08430-4. https://pubmed.ncbi.nlm.nih.gov/37133614/