Smarcd3, also known as BAF60C, is a member of the SWI/SNF protein complex. It plays crucial roles in epigenetic regulation, participating in various biological processes such as cell proliferation, myoblast differentiation, and the regulation of metabolic landscapes. It is associated with pathways like lipid and fatty acid metabolism, epithelial-mesenchymal transition (EMT), and cell cycle regulation [1,3,5,6].

In pancreatic cancer, diverse genetic mouse models and stage-specific Smarcd3 deletion revealed that Smarcd3 loss preferentially impacts established tumors, improving survival especially with chemotherapy. Mechanistically, it acts with FOXA1 to control lipid and fatty acid metabolism, programs related to therapy resistance and poor prognosis [1]. In medulloblastoma, it regulates Disabled 1 (DAB1)-mediated Reelin signalling in Purkinje cell migration and metastasis [2]. In gastric cancer, SMARCD3 overexpression promotes EMT, while its knockout leads to decreased proliferation, migration, and invasion [3]. In colorectal cancer, it may promote cancer metastasis through activation of cancer-associated fibroblasts (CAFs) via a positive feedback loop [4].

In conclusion, Smarcd3 is essential for multiple biological processes. Studies using gene knockout and conditional knockout mouse models have revealed its significant roles in pancreatic cancer, medulloblastoma, gastric cancer, and colorectal cancer, providing potential therapeutic targets for these diseases.

References:

1. Ferguson, L Paige, Gatchalian, Jovylyn, McDermott, Matthew L, Hargreaves, Diana C, Reya, Tannishtha. 2023. Smarcd3 is an epigenetic modulator of the metabolic landscape in pancreatic ductal adenocarcinoma. In Nature communications, 14, 292. doi:10.1038/s41467-023-35796-7. https://pubmed.ncbi.nlm.nih.gov/36653361/

2. Zou, Han, Poore, Bradley, Brown, Emily E, Taylor, Michael D, Hu, Baoli. 2023. A neurodevelopmental epigenetic programme mediated by SMARCD3-DAB1-Reelin signalling is hijacked to promote medulloblastoma metastasis. In Nature cell biology, 25, 493-507. doi:10.1038/s41556-023-01093-0. https://pubmed.ncbi.nlm.nih.gov/36849558/

3. Park, Sun Yi, Park, Ji-Ho, Yang, Jung Wook, Lee, Young-Joon, Jeong, Sang-Ho. 2024. SMARCD3 Overexpression Promotes Epithelial-Mesenchymal Transition in Gastric Cancer. In Cancers, 16, . doi:10.3390/cancers16122282. https://pubmed.ncbi.nlm.nih.gov/38927986/

4. Jiang, Ming, Wang, Huiju, Chen, Hong, Han, Yong. 2020. SMARCD3 is a potential prognostic marker and therapeutic target in CAFs. In Aging, 12, 20835-20861. doi:10.18632/aging.104102. https://pubmed.ncbi.nlm.nih.gov/33125346/

5. Zhang, Jing, Cai, Bolin, Ma, Manting, Zhang, Xiquan, Nie, Qinghua. 2022. LncRNA SMARCD3-OT1 Promotes Muscle Hypertrophy and Fast-Twitch Fiber Transformation via Enhancing SMARCD3X4 Expression. In International journal of molecular sciences, 23, . doi:10.3390/ijms23094510. https://pubmed.ncbi.nlm.nih.gov/35562902/

6. Tropée, Romain, de la Peña Avalos, Bárbara, Gough, Madeline, Duijf, Pascal H G, Dray, Eloïse. 2020. The SWI/SNF subunit SMARCD3 regulates cell cycle progression and predicts survival outcome in ER+ breast cancer. In Breast cancer research and treatment, 185, 601-614. doi:10.1007/s10549-020-05997-5. https://pubmed.ncbi.nlm.nih.gov/33180234/