Dock6, a guanine nucleotide exchange factor (GEF) for Rac1 and CDC42, plays significant roles in multiple biological processes. It is involved in pathways like WNT/β-catenin signaling, which are crucial for normal development and disease progression [1].

In gastric cancer, Dock6 is identified as an independent biomarker. Its elevated expression is associated with tumor size, invasion depth, lymph node metastasis, and poor patient survival. Ectopic expression promotes cancer stem cell characteristics and chemo-or radioresistance via Rac1 activation, while its depletion suppresses cancer progression [1]. In oral squamous cell cancer, Dock6 is upregulated, promoting cellular migration and invasion, and is also related to poor prognosis [3]. Mutations in Dock6 are responsible for an autosomal-recessive variant of Adams-Oliver syndrome, often associated with brain and eye anomalies [4]. Intrafamilial phenotypic variability exists in this syndrome related to Dock6 mutations [2].

In summary, Dock6 is a key regulator in several biological processes and disease conditions. Its role in promoting cancer progression in gastric and oral cancers, and its association with Adams-Oliver syndrome, highlight its importance in disease-related research. Functional studies, potentially including gene knockout or conditional knockout mouse models in the future, could further elucidate its molecular mechanisms in these diseases [1,2,3,4].

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/