Sec14l3, a member of the Sec14-like phosphatidylinositol transfer protein family, plays diverse roles in various biological processes. It is involved in pathways such as Wnt/β-catenin, VEGFR2 signaling, and Wnt/Ca2+ signaling, and is important for vasculogenesis, maintaining airway epithelial cell homeostasis, and lipid-related functions [2,4,5]. Genetic models like zebrafish have been valuable in studying its functions.

In breast cancer, Sec14l3 is underexpressed and acts as a tumor-suppressor through a Wnt/β-catenin-related mechanism. Overexpressing it inhibits cancer cell migration, invasion, and Wnt/β-catenin activation [1]. In zebrafish, sec14l3 depletion causes vascular defects, and it potentiates VEGFR2 signaling by preventing its dephosphorylation and facilitating endocytic trafficking [2]. In clear cell renal cell carcinoma, SEC14L3 is upregulated, and its knockdown suppresses cell proliferation, metastasis, and sunitinib resistance through an SEC14L3/RPS3/NFκB positive feedback loop [3].

In summary, Sec14l3 is crucial for normal biological functions and is involved in disease-related processes. Its study using genetic models has revealed its significance in cancer and vasculogenesis, providing insights into potential therapeutic targets for breast and renal cancers and understanding of vasculogenesis mechanisms.

References:

1. Zhu, Qing, Wan, Neng-Bin, Deng, Hong-Wu, Liu, Hao, He, Ying. 2022. SEC14L3 plays a tumor-suppressive role in breast cancer through a Wnt/β-catenin-related way. In Experimental cell research, 417, 113161. doi:10.1016/j.yexcr.2022.113161. https://pubmed.ncbi.nlm.nih.gov/35447102/

2. Gong, Bo, Li, Zhihao, Xiao, Wanghua, Meng, Anming, Jia, Shunji. 2019. Sec14l3 potentiates VEGFR2 signaling to regulate zebrafish vasculogenesis. In Nature communications, 10, 1606. doi:10.1038/s41467-019-09604-0. https://pubmed.ncbi.nlm.nih.gov/30962435/

3. Jiang, Ziming, Yang, Guangcan, Wang, Guangchun, Wang, Keyi, Peng, Bo. 2024. SEC14L3 knockdown inhibited clear cell renal cell carcinoma proliferation, metastasis and sunitinib resistance through an SEC14L3/RPS3/NFκB positive feedback loop. In Journal of experimental & clinical cancer research : CR, 43, 288. doi:10.1186/s13046-024-03206-5. https://pubmed.ncbi.nlm.nih.gov/39425205/

4. Shan, Lihua, Noritake, Shinobu, Fujiwara, Masatoshi, Yamashita, Keizo, Kawakami, Takao. . Sec14l3 is specifically expressed in mouse airway ciliated cells. In Inflammation, 35, 702-12. doi:10.1007/s10753-011-9363-z. https://pubmed.ncbi.nlm.nih.gov/21796385/

5. Gong, Bo, Shen, Weimin, Xiao, Wanghua, Meng, Anming, Jia, Shunji. 2017. The Sec14-like phosphatidylinositol transfer proteins Sec14l3/SEC14L2 act as GTPase proteins to mediate Wnt/Ca2+ signaling. In eLife, 6, . doi:10.7554/eLife.26362. https://pubmed.ncbi.nlm.nih.gov/28463110/