OSBPL3, an intracellular lipid receptor of the oxysterol-binding protein superfamily, participates in some pathological and physiological processes in tumor progression. It has been associated with regulating the actin cytoskeleton [6].

OSBPL3 is overexpressed in a variety of malignancies. In colorectal cancer (CRC), its high expression is associated with worse progression-free survival and overall survival, and is negatively correlated with tumor differentiation. KRAS mutations, detected in about 32.6% of CRC patients, are significantly associated with high OSBPL3 expression, and OSBPL3 expression is also significantly correlated with Ki-67 expression. Over-expression of OSBPL3 promotes CRC cell proliferation, invasion and metastasis both in vitro and in vivo, likely through activation of the RAS signaling pathway. Hypoxia induced factor 1 (HIF-1A) can regulate OSBPL3 expression by binding to its promoter [1,2]. In pancreatic cancer, high OSBPL3 expression is associated with immunosuppressive characteristics, such as reduced CD8+ T cell infiltration and increased immunosuppressive cell populations, and is linked to resistance to immunotherapy [3]. In hepatocellular carcinoma, upregulated OSBPL3 is observed in tumor tissues, especially in more advanced stages, and is associated with poor clinical outcomes [4]. In gastric cancer, OSBPL3 overexpression is detected in cancer cells, and knockdown of OSBPL3 reduces cell growth by inhibiting cell cycle progression, likely by activating the R-Ras/Akt signaling pathway [5].

In summary, OSBPL3 plays a crucial role in the development and progression of multiple cancers, including CRC, pancreatic, hepatocellular, and gastric cancers. Its overexpression promotes tumor growth, invasion, metastasis, and immunosuppression, mainly through activation of relevant signaling pathways. These findings from in vitro and in vivo studies suggest that OSBPL3 could be a potential therapeutic target for these cancers.

References:

1. Zhang, Min, Meng, Lei, Zhang, Zhaoxuan, Wang, Yuejing, He, Jie. 2022. The relationships of OSBPL3 expression with KI-67 expression and KRAS mutations in CRC: implications for diagnosis and prognosis. In BMC medical genomics, 15, 259. doi:10.1186/s12920-022-01402-w. https://pubmed.ncbi.nlm.nih.gov/36517805/

2. Jiao, Hong-Li, Weng, Bin-Shu, Yan, Shan-Shan, Ding, Yan-Qing, Ye, Ya-Ping. 2020. Upregulation of OSBPL3 by HIF1A promotes colorectal cancer progression through activation of RAS signaling pathway. In Cell death & disease, 11, 571. doi:10.1038/s41419-020-02793-3. https://pubmed.ncbi.nlm.nih.gov/32709922/

3. Sun, Qihui, Zhu, Xiaoqi, Zou, Qi, Xie, Keping, Liu, Jia. 2025. OSBPL3 modulates the immunosuppressive microenvironment and predicts therapeutic outcomes in pancreatic cancer. In Biology direct, 20, 5. doi:10.1186/s13062-025-00596-0. https://pubmed.ncbi.nlm.nih.gov/39789613/

4. Su, Yuanshuai, Xue, Chen, Gu, Xinyu, Zhang, Renfang, Li, Lanjuan. 2023. Integrated bioinformatics analysis reveals the function and prognostic value of OSBPL3 in hepatocellular carcinoma. In Heliyon, 9, e17223. doi:10.1016/j.heliyon.2023.e17223. https://pubmed.ncbi.nlm.nih.gov/37389070/

5. Hu, Qingjiang, Masuda, Takaaki, Koike, Kensuke, Oki, Eiji, Mimori, Koshi. 2021. Oxysterol binding protein-like 3 (OSBPL3) is a novel driver gene that promotes tumor growth in part through R-Ras/Akt signaling in gastric cancer. In Scientific reports, 11, 19178. doi:10.1038/s41598-021-98485-9. https://pubmed.ncbi.nlm.nih.gov/34584127/

6. Juszczak, Grzegorz R, Stankiewicz, Adrian M. 2017. Glucocorticoids, genes and brain function. In Progress in neuro-psychopharmacology & biological psychiatry, 82, 136-168. doi:10.1016/j.pnpbp.2017.11.020. https://pubmed.ncbi.nlm.nih.gov/29180230/