PLPP4, also known as PPAPDC1A, is a phospholipid phosphatase enzyme involved in the regulation of triacylglycerol metabolism [3]. It may play significant roles in multiple biological processes, and its study in genetic models can help uncover its functions.

In various cancers, PLPP4 has been implicated. In breast cancer, its up-regulation is observed, and knockdown of PLPP4 suppresses cell proliferation, migration, invasion, enhances apoptosis, and improves sensitivity to doxorubicin (DOX). The transcription factor CAPRIN1 can transcriptionally activate PLPP4 to promote breast cancer progression and inhibit DOX sensitivity [1]. In glioma and pancreatic adenocarcinoma, high expression of PLPP4 is associated with poor clinicopathological features and overall survival, and silencing PLPP4 inhibits cell proliferation, invasion, and migration [2]. In lung carcinoma, high PLPP4 expression correlates with poor clinicopathological features and survival, and silencing PLPP4 inhibits proliferation, cell cycle progression, and tumorigenesis, potentially via reducing intracellular Ca2+ influx [4].

In conclusion, PLPP4 is a key gene in lipid metabolism-related processes. Through gene-knockout or knockdown studies in cancer cells, it has been shown to play important roles in promoting the progression of breast, glioma, pancreatic, and lung cancers. Understanding PLPP4's functions may offer new therapeutic strategies for these cancer types.

References:

1. Yuan, Xiaorong, Yang, Xuejie. 2024. CAPRIN1 Transcriptionally Activated PLPP4 to Inhibit DOX Sensitivity and Promote Breast Cancer Progression. In Cell biochemistry and biophysics, , . doi:10.1007/s12013-024-01614-0. https://pubmed.ncbi.nlm.nih.gov/39556159/

2. Tian, Wenxiu, Wang, Ping, Wang, Zhimei, Dong, Junhong, Wang, Hongmei. 2021. Phospholipid Phosphatase 4 as a Driver of Malignant Glioma and Pancreatic Adenocarcinoma. In Frontiers in oncology, 11, 790676. doi:10.3389/fonc.2021.790676. https://pubmed.ncbi.nlm.nih.gov/34917513/

3. Soni, Sneha, Makwana, Sweta H, Bansal, Shivani, Kumari, Monika, Mandal, Chandi C. 2025. Lipid metabolism associated PLPP4 gene drives oncogenic and adipogenic potential in breast cancer cells. In Biochimica et biophysica acta. Molecular and cell biology of lipids, 1870, 159609. doi:10.1016/j.bbalip.2025.159609. https://pubmed.ncbi.nlm.nih.gov/40187483/

4. Zhang, Xin, Zhang, Lan, Lin, Bihua, Ren, Dong, Huang, Yanming. 2017. Phospholipid Phosphatase 4 promotes proliferation and tumorigenesis, and activates Ca2+-permeable Cationic Channel in lung carcinoma cells. In Molecular cancer, 16, 147. doi:10.1186/s12943-017-0717-5. https://pubmed.ncbi.nlm.nih.gov/28851360/