Surf4, also known as Surfeit locus protein 4, is a polytopic transmembrane protein mainly located in the endoplasmic reticulum (ER) membrane. It functions as a cargo receptor, mediating the transport of various cargos from the ER to the Golgi apparatus via COPII-coated vesicles or specific vesicles, and also participates in retrograde transportation from the Golgi to the ER through COPI-coated vesicles. This protein is involved in ER-Golgi protein trafficking, lipid metabolism, cell proliferation, and migration, and is crucial for multiple physiological and pathophysiological processes [1].

Gene knockout (KO) and conditional knockout (CKO) mouse models have significantly advanced our understanding of Surf4's functions. Homozygous Surf4 -/- mice show embryonic lethality between embryonic days 3.5 and 9.5, suggesting its essential role in early embryonic development [5]. Intestinal-specific Surf4 knockout (Surf4IKO) mice display reduced body weight, increased mortality, impaired fat absorption and secretion, and lipid accumulation in enterocytes. This indicates that intestinal Surf4 is vital for lipid absorption and chylomicron secretion [2]. Hepatic Surf4 deficiency in mice (Surf4 LKO) reduces serum amyloid A1 secretion and attenuates liver fibrosis, suggesting its role in liver fibrosis progression [3]. In breast cancer, high Surf4 expression in tumor tissues is associated with poor prognosis, and it promotes the proliferation and migration of 4T1 cells [4]. In ovarian cancer cells, knockdown of Surf4 reduces stem-like properties and increases sensitivity to chemotherapeutic drugs [6].

In summary, Surf4 is crucial for cargo trafficking, lipid metabolism, and early embryonic development. KO/CKO mouse models have revealed its role in various disease-related processes such as liver fibrosis, breast cancer, and ovarian cancer, providing insights into potential therapeutic targets. These models are valuable research tools for in-vivo functional studies of Surf4.

References:

1. Shen, Yishi, Gu, Hong-Mei, Qin, Shucun, Zhang, Da-Wei. . Surf4, cargo trafficking, lipid metabolism, and therapeutic implications. In Journal of molecular cell biology, 14, . doi:10.1093/jmcb/mjac063. https://pubmed.ncbi.nlm.nih.gov/36574593/

2. Tao, Geru, Wang, Hao, Shen, Yishi, Qin, Shucun, Zhang, Da-Wei. 2023. Surf4 (Surfeit Locus Protein 4) Deficiency Reduces Intestinal Lipid Absorption and Secretion and Decreases Metabolism in Mice. In Arteriosclerosis, thrombosis, and vascular biology, 43, 562-580. doi:10.1161/ATVBAHA.123.318980. https://pubmed.ncbi.nlm.nih.gov/36756879/

3. Wang, Bingxiang, Li, Huili, Gill, Govind, Qin, Shucun, Zhang, Da-Wei. 2024. Hepatic Surf4 Deficiency Impairs Serum Amyloid A1 Secretion and Attenuates Liver Fibrosis in Mice. In Research (Washington, D.C.), 7, 0435. doi:10.34133/research.0435. https://pubmed.ncbi.nlm.nih.gov/39105051/

4. Zhai, Jingtong, Han, Jiashu, Li, Cong, Ma, Fei, Xu, Binghe. 2022. High SURF4 expression is associated with poor prognosis of breast cancer. In Aging, 14, 9317-9337. doi:10.18632/aging.204409. https://pubmed.ncbi.nlm.nih.gov/36446386/

5. Emmer, Brian T, Lascuna, Paul J, Tang, Vi T, Khoriaty, Rami, Ginsburg, David. 2020. Murine Surf4 is essential for early embryonic development. In PloS one, 15, e0227450. doi:10.1371/journal.pone.0227450. https://pubmed.ncbi.nlm.nih.gov/31978056/

6. Yue, Yongfang, Xia, Lili, Xu, Shanshan, Lu, Weiguo, Xie, Xing. 2020. SURF4 maintains stem-like properties via BIRC3 in ovarian cancer cells. In Journal of gynecologic oncology, 31, e46. doi:10.3802/jgo.2020.31.e46. https://pubmed.ncbi.nlm.nih.gov/32026660/