Slc22a18, the solute carrier family 22 member 18, is an orphan transporter with an unknown endogenous substrate. It has been proposed to be involved in lipid metabolism-related pathways and may play a role in tumor-related processes [3,4]. Genetic models like knockout mice are valuable for studying its functions.

In gene-knockout mouse models, Slc22a18 knockout mice grew normally but showed decreased hepatic triglyceride content under refeeding conditions, reduced epididymal fat mass, and lower liver weight in leptin-deficient states, indicating its positive effect on lipid accumulation in vivo [1]. In HepG2 cells, knockdown of Slc22a18 impaired lipid metabolism, suppressed lipid degradation, and increased cell invasiveness [3]. In colorectal cancer, low SLC22A18-expressing cells were less sensitive to oxaliplatin, and its down-regulation was associated with worse survival, and the ERK pathway was involved in SLC22A18-related oxaliplatin resistance [2]. Also, missense variants of SLC22A18 in colon cancer cells led to higher proliferation, migration, and invasion compared to the wild-type [5].

In summary, Slc22a18 has a positive impact on lipid accumulation in vivo. Its role in cancer, especially in colorectal cancer and glioma, is significant as its down-regulation is associated with poor prognosis and drug resistance. The use of knockout mouse models and cell-based knockdown experiments has been crucial in uncovering these functions, providing insights into potential disease mechanisms and therapeutic targets.

References:

1. Yamamoto, Takashi, Iizuka, Yoko, Izumi-Yamamoto, Kozue, Fujita, Toshiro, Gotoda, Takanari. 2024. Overexpression of Slc22a18 facilitates fat accumulation in mice. In Biochemical and biophysical research communications, 712-713, 149922. doi:10.1016/j.bbrc.2024.149922. https://pubmed.ncbi.nlm.nih.gov/38626531/

2. Kim, Tae Won, Pyo, Dae Hee, Ko, Eunbyeol, Lee, Woo Yong, Cho, Yong Beom. 2022. Expression of SLC22A18 regulates oxaliplatin resistance by modulating the ERK pathway in colorectal cancer. In American journal of cancer research, 12, 1393-1408. doi:. https://pubmed.ncbi.nlm.nih.gov/35411243/

3. Ito, Shingo, Honda, Gentaro, Fujino, Yu, Hirayama-Kurogi, Mio, Ohtsuki, Sumio. 2019. Knockdown of Orphan Transporter SLC22A18 Impairs Lipid Metabolism and Increases Invasiveness of HepG2 Cells. In Pharmaceutical research, 36, 39. doi:10.1007/s11095-018-2565-4. https://pubmed.ncbi.nlm.nih.gov/30635741/

4. Jung, Yeonjoo, Jun, Yukyung, Lee, Hee-Young, Lee, Sanghyuk, Kim, Jaesang. . Characterization of SLC22A18 as a tumor suppressor and novel biomarker in colorectal cancer. In Oncotarget, 6, 25368-80. doi:10.18632/oncotarget.4681. https://pubmed.ncbi.nlm.nih.gov/26196590/

5. Song, Hyo Sook, Ha, Seung Yeon, Kim, Jin-Young, Kim, Minsuk, Choi, Ji Ha. 2024. The effect of genetic variants of SLC22A18 on proliferation, migration, and invasion of colon cancer cells. In Scientific reports, 14, 3925. doi:10.1038/s41598-024-54658-w. https://pubmed.ncbi.nlm.nih.gov/38366023/