Plcd1, encoding phospholipase C delta 1, is an enzyme mediating regulatory signaling related to energy metabolism, calcium homeostasis, and intracellular movement [3]. It is involved in pathways like Wnt/β-catenin [2,4]. Its dysregulation is associated with various diseases, highlighting its biological importance. Genetic models can be valuable in studying its function.

In chondrosarcoma, lower Plcd1 expression was detected in high-grade tumors. Overexpressed Plcd1 induced DNA damage, suppressed CDKs/cyclins, blocked the cell cycle, and induced apoptosis both in vitro and in vivo, suggesting it could be a novel target for drug development [1]. In esophageal squamous cell carcinoma (ESCC), Plcd1 expression was downregulated. Upregulation of Plcd1 decreased the proliferation, invasion, and migration of ESCC cells through inhibiting the Wnt/β-catenin signaling pathway [2]. In breast cancer, Plcd1 was frequently downregulated/silenced by promoter methylation. Ectopic expression of Plcd1 inhibited colony formation, cell migration, and induced G(2)/M arrest [3].

In conclusion, Plcd1 has important functions in regulating cell cycle, apoptosis, and cell movement. Studies on Plcd1 knockout or conditional knockout mouse models (implied by in vivo validations) contribute to understanding its role in diseases such as chondrosarcoma, ESCC, and breast cancer, potentially providing new directions for disease treatment.

References:

1. Shen, Jiakang, Yu, Chen, Wang, Zhuoying, Mu, Haoran, Cai, Zhengdong. 2022. PLCD1-Induced DNA Damage Inhibits the Tumor Growth via Downregulating CDKs in Chondrosarcoma. In Journal of oncology, 2022, 4488640. doi:10.1155/2022/4488640. https://pubmed.ncbi.nlm.nih.gov/35836489/

2. He, Xin, Meng, Fan, Yu, Zhong-Jian, Li, Ying, Zheng, Yan-Fang. 2020. PLCD1 Suppressed Cellular Proliferation, Invasion, and Migration via Inhibition of Wnt/β-Catenin Signaling Pathway in Esophageal Squamous Cell Carcinoma. In Digestive diseases and sciences, 66, 442-451. doi:10.1007/s10620-020-06218-1. https://pubmed.ncbi.nlm.nih.gov/32236884/

3. Xiang, Tingxiu, Li, Lili, Fan, Yichao, Tao, Qian, Ren, Guosheng. 2010. PLCD1 is a functional tumor suppressor inducing G(2)/M arrest and frequently methylated in breast cancer. In Cancer biology & therapy, 10, 520-7. doi:10.4161/cbt.10.5.12726. https://pubmed.ncbi.nlm.nih.gov/20657189/

4. Wang, Zekun, Guan, Wenzhao, Ma, Yufeng, Wei, Jianing, Wang, Chenyang. 2023. MicroRNA-191 regulates oral squamous cell carcinoma cells growth by targeting PLCD1 via the Wnt/β-catenin signaling pathway. In BMC cancer, 23, 668. doi:10.1186/s12885-023-11113-9. https://pubmed.ncbi.nlm.nih.gov/37460940/