Strip2, also known as Fam40b, is a core component of the striatin-interacting phosphatase and kinase (STRIPAK) complexes. It is involved in crucial biological processes such as cell growth, proliferation, migration, and differentiation [1,2,3,4,5,6]. It participates in multiple signaling pathways, like the PI3K/AKT/mTOR/MYC pathway [3], and is of great biological importance in embryonic stem cell differentiation and tumor-related processes. Genetic models, especially gene-knockout (KO) or conditional-knockout (CKO) mouse models, can be valuable for studying Strip2.

In non-small cell lung cancer (NSCLC), knockdown of Strip2 suppressed tumor growth and metastasis in vitro and in vivo. Mechanistically, P300/CBP-mediated H3K27 acetylation activation in the Strip2 promoter induced its transcription, which interacted with IGF2BP3 and upregulated IGF2BP3 transcription. The Strip2-IGF2BP3 axis then stimulated m6A modification of TMBIM6 mRNA and enhanced TMBIM6 stability, affecting NSCLC cell proliferation, migration, and invasion [1]. In vascular smooth muscle cells, Strip2 depletion suppressed cell proliferation and migration, related to decreased MMP-2/MMP-9 expression and inactivation of P38 and AKT [4]. In lung adenocarcinoma, Strip2 silencing reduced tumor growth and lung metastasis in xenograft models, and it promoted cell proliferation, invasion, and migration by boosting the PI3K/AKT/mTOR/MYC cascades [3]. In gastric cancer, microRNA-30c-2-3p targeted Strip2 to suppress malignant progression of cancer cells [7].

In conclusion, Strip2 plays essential roles in processes like embryonic stem cell differentiation and tumor-related biological functions. Model-based research, especially KO or CKO mouse models (if applicable in the future), can further reveal its functions in diseases such as NSCLC, lung adenocarcinoma, and gastric cancer, providing potential directions for understanding disease mechanisms and developing therapeutic strategies.

References:

1. Zhang, Xilin, Chen, Qiuqiang, He, Ying, Tang, Chengwu, Dong, Zhaohui. 2023. STRIP2 motivates non-small cell lung cancer progression by modulating the TMBIM6 stability through IGF2BP3 dependent. In Journal of experimental & clinical cancer research : CR, 42, 19. doi:10.1186/s13046-022-02573-1. https://pubmed.ncbi.nlm.nih.gov/36639675/

2. Srinivasan, Sureshkumar Perumal, Nemade, Harshal, Cherianidou, Anna, Rada-Iglesias, Alvaro, Sachinidis, Agapios. 2022. Epigenetic mechanisms of Strip2 in differentiation of pluripotent stem cells. In Cell death discovery, 8, 447. doi:10.1038/s41420-022-01237-5. https://pubmed.ncbi.nlm.nih.gov/36335090/

3. Pan, Junfan, Zhang, Yuan, He, Liu, Zhang, Jing, Xu, Yiquan. 2024. STRIP2 is regulated by the transcription factor Sp1 and promotes lung adenocarcinoma progression via activating the PI3K/AKT/mTOR/MYC signaling pathway. In Genomics, 116, 110923. doi:10.1016/j.ygeno.2024.110923. https://pubmed.ncbi.nlm.nih.gov/39191354/

4. Dai, Li, Zhou, Jun, Li, Tiantian, Zhu, Chao, Li, Shengnan. 2019. STRIP2 silencing inhibits vascular smooth muscle cell proliferation and migration via P38-AKT-MMP-2 signaling pathway. In Journal of cellular physiology, 234, 22463-22476. doi:10.1002/jcp.28810. https://pubmed.ncbi.nlm.nih.gov/31093976/

5. Qiu, Li-Min, Sun, Yun-Hao, Chen, Ting-Ting, Chen, Jin-Jin, Ma, Hai-Tao. 2020. STRIP2, a member of the striatin-interacting phosphatase and kinase complex, is implicated in lung adenocarcinoma cell growth and migration. In FEBS open bio, 10, 351-361. doi:10.1002/2211-5463.12785. https://pubmed.ncbi.nlm.nih.gov/31901223/

6. Jaradat, Jaber H, Masharqa, Ghaith, Al-Shnaikat, Raneem Ghazi, Al-Nusairi, Ahmed M, Saeed, Anwaar. . The Multifaceted Role of Striatin-interacting Protein 2 (STRIP2) in Disease Pathogenesis and Cancer Progression. In Anticancer research, 44, 5169-5174. doi:10.21873/anticanres.17342. https://pubmed.ncbi.nlm.nih.gov/39626932/

7. Wu, Junfei, Lu, Guochun, Zhou, Shengkun, Jin, Zier, Fang, Fu. . MicroRNA-30c-2-3p targets STRIP2 to suppress malignant progression of gastric cancer cells. In Journal of biochemistry, 171, 451-457. doi:10.1093/jb/mvac006. https://pubmed.ncbi.nlm.nih.gov/35106560/