Ppfia4, also known as liprin-alpha-4, is a gene that has been implicated in various biological processes and diseases. It encodes a protein that may be involved in processes like cell-cell adhesion and signal transduction pathways [7]. The PPFIA family, including Ppfia4, consists of specific domains such as PFIH1-4 and SAM domains, which may be involved in protein-protein interactions [7].

In cancer research, Ppfia4 has been shown to play significant roles. In castration-resistant prostate cancer, Ppfia4 localizes to mitochondria and interacts with MTHFD2, enhancing mitochondrial metabolism and promoting tumor growth. Androgen deprivation increases its mitochondrial translocation and interaction with MTHFD2, leading to increased NADPH synthesis and protection against mitochondrial dysfunction [1]. In esophageal, colon, and ovarian cancers, Ppfia4 promotes cell proliferation, migration, and glycolysis. Inhibition of Ppfia4 in these cancer cells leads to decreased invasion, migration, and glycolysis [2,3,4]. In colorectal cancer, Ppfia4 expression is associated with disease development, and it may be a potential prognostic marker. High Ppfia4 levels are related to poor survival of patients, and it is upregulated in poorly differentiated and metastatic tissues [3,5]. Also, in colorectal adenocarcinoma, the lncRNA MNX1-AS1/PPFIA4 axis activates the AKT/HIF-1α signaling pathway to promote cell stemness [6].

In conclusion, Ppfia4 plays crucial roles in promoting cancer-related processes such as mitochondrial metabolism, cell proliferation, migration, and glycolysis in multiple cancer types. These findings from various in vitro and in vivo studies, including potential mouse models implied in functional research, contribute to understanding cancer mechanisms and suggest Ppfia4 as a potential therapeutic target in cancer treatment [1-5,7].

References:

1. Zhao, Ru, Feng, Tingting, Gao, Lin, Wang, Lin, Han, Bo. 2022. PPFIA4 promotes castration-resistant prostate cancer by enhancing mitochondrial metabolism through MTHFD2. In Journal of experimental & clinical cancer research : CR, 41, 125. doi:10.1186/s13046-022-02331-3. https://pubmed.ncbi.nlm.nih.gov/35382861/

2. He, Yingying, Lu, Dingyu, Cheng, Hao, Wu, Fei, Chen, Zhaohong. . PPFIA4 Promotes Proliferation, Migration and Glycolysis of Esophageal Cancer Cells. In Annals of clinical and laboratory science, 53, 840-846. doi:. https://pubmed.ncbi.nlm.nih.gov/38182152/

3. Huang, Jia, Yang, Meiling, Liu, Zhaoxia, Cao, Ting, Yang, Xuefeng. 2021. PPFIA4 Promotes Colon Cancer Cell Proliferation and Migration by Enhancing Tumor Glycolysis. In Frontiers in oncology, 11, 653200. doi:10.3389/fonc.2021.653200. https://pubmed.ncbi.nlm.nih.gov/34094943/

4. Tan, Shu, Yu, Hao, Xu, Ye, Zhao, Yue, Lou, Ge. 2023. Hypoxia-induced PPFIA4 accelerates the progression of ovarian cancer through glucose metabolic reprogramming. In Medical oncology (Northwood, London, England), 40, 272. doi:10.1007/s12032-023-02144-0. https://pubmed.ncbi.nlm.nih.gov/37596446/

5. Fu, Fangmei, Niu, Rui, Zheng, Minying, Fu, Wenzheng, Zhang, Shiwu. 2023. Clinicopathological Significances and Prognostic Value of PPFIA4 in Colorectal Cancer. In Journal of Cancer, 14, 24-34. doi:10.7150/jca.78634. https://pubmed.ncbi.nlm.nih.gov/36605492/

6. Sun, Qi, Gui, Zhifu, Zhao, Zhenguo, Zhao, Wei, Hu, Hao. 2022. Overexpression of LncRNA MNX1-AS1/PPFIA4 Activates AKT/HIF-1α Signal Pathway to Promote Stemness of Colorectal Adenocarcinoma Cells. In Journal of oncology, 2022, 8303409. doi:10.1155/2022/8303409. https://pubmed.ncbi.nlm.nih.gov/36226248/

7. Katoh, Masuko, Katoh, Masaru. . Identification and characterization of human PPFIA4 gene in silico. In International journal of molecular medicine, 12, 1009-14. doi:. https://pubmed.ncbi.nlm.nih.gov/14612982/