Slc37a1-KO Mouse

Slc37a1, also known as G3PP, belongs to the SLC37 family of sugar-phosphate/phosphate exchangers and is localized in the endoplasmic reticulum membrane. It functions as a Pi-linked glucose-6-phosphate (G6P) antiporter, catalyzing G6P:Pi and Pi:Pi exchanges, and is also thought to transport glycerol-3-phosphate [2,3,4,5]. It may be involved in phospholipid biosynthesis as glycerol-3-phosphate is a fundamental substrate in this process, and it has potential implications in lipid biosynthesis in cancer cell lines [1,2].

In breast cancer cells, epidermal growth factor (EGF) transactivates the Slc37a1 promoter sequence and induces its mRNA and protein expression through the EGFR/MAPK/Fos transduction pathway. This was demonstrated in both ER-negative SkBr3 breast cancer cells and ER-positive endometrial Ishikawa tumor cells, suggesting its role in the stimulatory action of EGF in breast cancer cells [1]. In colorectal cancer, upregulated Slc37a1 expression was significantly associated with positive venous invasion, liver metastasis, and poor overall survival time, indicating its involvement in the hematogenous metastasis of CRC [6].

In conclusion, Slc37a1 is an important exchanger in the endoplasmic reticulum with functions related to sugar-phosphate and glycerol-3-phosphate transport, potentially playing roles in phospholipid and lipid biosynthesis. Its dysregulation is associated with certain cancers, such as breast and colorectal cancer, highlighting its significance in understanding cancer-related biological processes and potentially guiding future therapeutic strategies.

References:

1. Iacopetta, Domenico, Lappano, Rosamaria, Cappello, Anna Rita, Maggiolini, Marcello, Dolce, Vincenza. 2009. SLC37A1 gene expression is up-regulated by epidermal growth factor in breast cancer cells. In Breast cancer research and treatment, 122, 755-64. doi:10.1007/s10549-009-0620-x. https://pubmed.ncbi.nlm.nih.gov/19894109/

2. Cappello, Anna Rita, Curcio, Rosita, Lappano, Rosamaria, Maggiolini, Marcello, Dolce, Vincenza. 2018. The Physiopathological Role of the Exchangers Belonging to the SLC37 Family. In Frontiers in chemistry, 6, 122. doi:10.3389/fchem.2018.00122. https://pubmed.ncbi.nlm.nih.gov/29719821/

3. Pan, Chi-Jiunn, Chen, Shih-Yin, Jun, Hyun Sik, Mansfield, Brian C, Chou, Janice Y. 2011. SLC37A1 and SLC37A2 are phosphate-linked, glucose-6-phosphate antiporters. In PloS one, 6, e23157. doi:10.1371/journal.pone.0023157. https://pubmed.ncbi.nlm.nih.gov/21949678/

4. Chou, Janice Y, Mansfield, Brian C. . The SLC37 family of sugar-phosphate/phosphate exchangers. In Current topics in membranes, 73, 357-82. doi:10.1016/B978-0-12-800223-0.00010-4. https://pubmed.ncbi.nlm.nih.gov/24745989/

5. Chou, Janice Y, Sik Jun, Hyun, Mansfield, Brian C. . The SLC37 family of phosphate-linked sugar phosphate antiporters. In Molecular aspects of medicine, 34, 601-11. doi:10.1016/j.mam.2012.05.010. https://pubmed.ncbi.nlm.nih.gov/23506893/

6. Kikuchi, Daiki, Saito, Motonobu, Saito, Katsuharu, Ohki, Shinji, Takenoshita, Seiichi. 2017. Upregulated solute carrier family 37 member 1 in colorectal cancer is associated with poor patient outcome and metastasis. In Oncology letters, 15, 2065-2072. doi:10.3892/ol.2017.7559. https://pubmed.ncbi.nlm.nih.gov/29434906/