SYPL1, short for synaptophysin-like 1, is a neuroendocrine-related transmembrane protein. It is involved in vesicle-related pathways, which are crucial for various biological processes. Its functions are significant in sperm development and male fertility, as well as in the context of multiple cancers [1-8].

Genetic ablation of SYPL1 in mice shows that it is essential for the formation and accumulation of saccular elements in the sperm cytoplasmic droplet. These SYPL1-derived Golgi vesicles are critical for segregating key metabolic enzymes in late spermatids and epididymal sperm, which are required for sperm development and male fertility [1]. In pancreatic ductal adenocarcinoma (PDAC), gain-and loss-of-function experiments indicate that SYPL1 promotes cell proliferation and protects cells from apoptosis by suppressing ROS-induced ERK activation [2]. In colorectal cancer, both serum and fecal SYPL1 levels are significantly higher in patients compared to controls and adenoma patients, suggesting its potential as a biomarker for diagnosis, early detection, prognosis prediction, and therapeutic effect monitoring [3,4]. In hepatocellular carcinoma, SYPL1 overexpression is closely associated with malignant clinicopathologic features, epithelial-mesenchymal transition, and poor prognosis [5]. In oral squamous cell carcinoma, the YY1/Kcnq1ot1/miR-506-3p/SYPL1 axis affects cell progression [6]. In glioblastomas, SYPL1 is among the genes with increased expression in cells with high PRNP/PrPC levels, related to enhanced vesicle dynamics [7]. In breast cancer, non-coding mutations in SYPL1 were found in Nigerian patients, highlighting ethnic-driven somatic evolution [8].

In summary, SYPL1 plays essential roles in sperm cytoplasmic droplet formation for male fertility and is closely associated with the development and prognosis of multiple cancers. The use of mouse models, especially SYPL1 KO models, has been crucial in revealing these functions, providing valuable insights into male reproductive biology and cancer-related research.

References:

1. Liu, Jiali, Hermo, Louis, Ding, Deqiang, Hess, Rex A, Chen, Chen. 2023. SYPL1 defines a vesicular pathway essential for sperm cytoplasmic droplet formation and male fertility. In Nature communications, 14, 5113. doi:10.1038/s41467-023-40862-1. https://pubmed.ncbi.nlm.nih.gov/37607933/

2. Song, Yunda, Sun, Xuesong, Duan, Fangting, Wang, Jun, Li, Shengping. 2020. SYPL1 Inhibits Apoptosis in Pancreatic Ductal Adenocarcinoma via Suppression of ROS-Induced ERK Activation. In Frontiers in oncology, 10, 1482. doi:10.3389/fonc.2020.01482. https://pubmed.ncbi.nlm.nih.gov/33042794/

3. Shu, Tao, Wu, Kaiwen, Guo, Yuanbiao, Liu, Lei, Sun, Xiaobin. 2022. Evaluation of fecal SYPL1 as a diagnostic biomarker in colorectal cancer. In Clinical biochemistry, 103, 8-15. doi:10.1016/j.clinbiochem.2022.02.009. https://pubmed.ncbi.nlm.nih.gov/35218739/

4. Liu, Lei, He, Qiao, Li, Yan, Song, Xiaoyu, Guo, Yuanbiao. 2020. Serum SYPL1 is a promising diagnostic biomarker for colorectal cancer. In Clinica chimica acta; international journal of clinical chemistry, 509, 36-42. doi:10.1016/j.cca.2020.05.048. https://pubmed.ncbi.nlm.nih.gov/32502495/

5. Chen, Dong-Han, Wu, Qiu-Wan, Li, Xiu-Dong, Wang, Shuang-Jia, Zhang, Zhi-Ming. 2017. SYPL1 overexpression predicts poor prognosis of hepatocellular carcinoma and associates with epithelial-mesenchymal transition. In Oncology reports, 38, 1533-1542. doi:10.3892/or.2017.5843. https://pubmed.ncbi.nlm.nih.gov/28731154/

6. Ding, Yi, Duan, Heng, Lin, Jian, Zhang, Xuanxuan. 2022. YY1 accelerates oral squamous cell carcinoma progression through long non-coding RNA Kcnq1ot1/microRNA-506-3p/SYPL1 axis. In Journal of ovarian research, 15, 77. doi:10.1186/s13048-022-01000-5. https://pubmed.ncbi.nlm.nih.gov/35778739/

7. Boccacino, Jacqueline Marcia, Dos Santos Peixoto, Rafael, Fernandes, Camila Felix de Lima, da Rocha, Edroaldo Lummertz, Lopes, Marilene Hohmuth. 2024. Integrated transcriptomics uncovers an enhanced association between the prion protein gene expression and vesicle dynamics signatures in glioblastomas. In BMC cancer, 24, 199. doi:10.1186/s12885-024-11914-6. https://pubmed.ncbi.nlm.nih.gov/38347462/

8. Ansari-Pour, Naser, Zheng, Yonglan, Yoshimatsu, Toshio F, Wedge, David C, Olopade, Olufunmilayo I. 2021. Whole-genome analysis of Nigerian patients with breast cancer reveals ethnic-driven somatic evolution and distinct genomic subtypes. In Nature communications, 12, 6946. doi:10.1038/s41467-021-27079-w. https://pubmed.ncbi.nlm.nih.gov/34836952/