DACT3, also known as dishevelled binding antagonist of beta catenin 3, is a key negative regulator of the Wnt/β -catenin signaling pathway [1,2,3,4,5,6]. This pathway is crucial for various biological processes such as cell proliferation, differentiation, and apoptosis. Dysregulation of Wnt/β -catenin signaling is often associated with cancer development, highlighting the biological importance of DACT3 in maintaining normal cellular functions. Genetic models, like gene knockout models, can be valuable for further studying DACT3's functions.

In acute myeloid leukemia (AML), low DACT3 levels were associated with shorter survival rates. Upregulation of DACT3 repressed cellular proliferation, promoted cell cycle arrest and apoptosis of AML cells by decreasing levels of DVL2, phospho-GSK-3β, and active β-catenin, thus suppressing Wnt/β-catenin-mediated transcriptional activity [1]. In non-small cell lung cancer (NSCLC), Dact3 expression was reduced, and its low expression was correlated with lymph node metastasis and poor prognosis. Dact3 transfection decreased c-Myb expression, Wnt/β-catenin signaling activity, and cell invasive and proliferative capacity [3]. In glioma, DACT3 expression was decreased in tissues. Overexpression of DACT3 suppressed the proliferation, invasion, and migration of glioma cells, increased cell adhesion, and inhibited the Notch1 signaling pathway by downregulating β-catenin expression [6].

In conclusion, DACT3 plays essential roles in suppressing tumor progression in multiple cancer types, including AML, NSCLC, and glioma, mainly through its regulation of the Wnt/β-catenin signaling pathway. The study of DACT3 using gene-knockout or related models contributes to understanding the mechanisms of cancer development and may provide potential therapeutic targets for these diseases.

References:

1. Gao, Qiuying, Hou, Limin, Wang, Hui, Xun, Liru. 2022. DACT3 has a tumor-inhibiting role in acute myeloid leukemia via the suppression of Wnt/β-catenin signaling by DVL2. In Journal of biochemical and molecular toxicology, 36, e23014. doi:10.1002/jbt.23014. https://pubmed.ncbi.nlm.nih.gov/35187752/

2. Kim, Soo Jin, Kim, Suntae, Choi, Yong June, Kim, U Ji, Kang, Keon Wook. 2022. CKD-581 Downregulates Wnt/β-Catenin Pathway by DACT3 Induction in Hematologic Malignancy. In Biomolecules & therapeutics, 30, 435-446. doi:10.4062/biomolther.2022.022. https://pubmed.ncbi.nlm.nih.gov/35794797/

3. Zhao, Huanyu, Yang, Lianhe, Han, Yang, Wang, Enhua, Wu, Guangping. 2017. Dact3 inhibits the malignant phenotype of non-small cell lung cancer through downregulation of c-Myb. In International journal of clinical and experimental pathology, 10, 11580-11587. doi:. https://pubmed.ncbi.nlm.nih.gov/31966514/

4. Jiang, Xia, Tan, Jing, Li, Jingsong, Cheyette, Benjamin N R, Yu, Qiang. . DACT3 is an epigenetic regulator of Wnt/beta-catenin signaling in colorectal cancer and is a therapeutic target of histone modifications. In Cancer cell, 13, 529-41. doi:10.1016/j.ccr.2008.04.019. https://pubmed.ncbi.nlm.nih.gov/18538736/

5. Ren, Yanli, Chen, Yujie, Liang, Xue, Pan, Wenting, Yang, Ming. 2017. MiRNA-638 promotes autophagy and malignant phenotypes of cancer cells via directly suppressing DACT3. In Cancer letters, 390, 126-136. doi:10.1016/j.canlet.2017.01.009. https://pubmed.ncbi.nlm.nih.gov/28108314/

6. Yue, Jianhe, Zhang, Jiqin, Huan, Renzheng, Tan, Ying, Cheng, Yuan. 2023. Dishevelled-associated antagonist of β-catenin homolog 3 (DACT3) suppresses glioma progression though Notch1 signaling pathway in β-catenin-dependent manner. In Heliyon, 10, e23511. doi:10.1016/j.heliyon.2023.e23511. https://pubmed.ncbi.nlm.nih.gov/38230242/