Strn4, also known as Striatin 4 or Zinedin, is a scaffolding protein belonging to the mammalian STRN family. It consists of multiple functional signaling domains and is involved in various biological processes. Strn4 has been associated with the Hippo pathway and protein phosphatase 2A (PP2A)-related signaling, which are crucial for development, organ size regulation, tissue homeostasis, and cancer [4,5].

In tumor-associated macrophages, PP2A with its specific B regulatory subunit Strn4 negatively regulates STING-Type I IFN signaling. Macrophage-specific PP2A deficiency in mice led to reduced tumor progression, with changes in the tumor microenvironment such as decreased immunosuppressive and increased IFN-activated macrophages and CD8+ T cells [1]. In cancer cell lines and in vivo mouse models, silencing of Strn4 suppresses proliferation, migration, invasion, and anchorage-independent growth of cancer cells. It also increases the sensitivity of pancreatic cancer cells to gemcitabine and suppresses the proliferation and metastasis of cancer cells in mice [3]. In addition, in non-small cell lung cancer, miR-29b inhibits cancer progression by targeting Strn4, and down-regulation of Strn4 in vitro and in vivo suppresses cellular proliferation and delays tumor progression [2].

In conclusion, Strn4 plays a significant role in tumor progression, especially in the regulation of immune-related signaling in tumor-associated macrophages and the malignant characteristics of cancer cells. Studies using gene knockout or knockdown models in mice and cell lines have revealed its importance in these disease-related biological processes, providing potential therapeutic targets for cancer treatment.

References:

1. Ho, Winson S, Mondal, Isha, Xu, Beisi, Meng, Zhipeng, Lu, Rongze Olivia. 2023. PP2Ac/STRN4 negatively regulates STING-type I IFN signaling in tumor-associated macrophages. In The Journal of clinical investigation, 133, . doi:10.1172/JCI162139. https://pubmed.ncbi.nlm.nih.gov/36757811/

2. Xie, Yuping, Zhao, Fen, Zhang, Ping, Duan, Ping, Shen, Yangmei. 2019. miR-29b inhibits non-small cell lung cancer progression by targeting STRN4. In Human cell, 33, 220-231. doi:10.1007/s13577-019-00305-w. https://pubmed.ncbi.nlm.nih.gov/31813135/

3. Wong, Meihong, Hyodo, Toshinori, Asano, Eri, Hamaguchi, Michinari, Senga, Takeshi. 2014. Silencing of STRN4 suppresses the malignant characteristics of cancer cells. In Cancer science, 105, 1526-32. doi:10.1111/cas.12541. https://pubmed.ncbi.nlm.nih.gov/25250919/

4. Seo, Gayoung, Han, Han, Vargas, Rebecca Elizabeth, Li, Xu, Wang, Wenqi. . MAP4K Interactome Reveals STRN4 as a Key STRIPAK Complex Component in Hippo Pathway Regulation. In Cell reports, 32, 107860. doi:10.1016/j.celrep.2020.107860. https://pubmed.ncbi.nlm.nih.gov/32640226/

5. Seo, Gayoung, Mckinley, Joshua, Wang, Wenqi. 2023. MAP4K2 connects the Hippo pathway to autophagy in response to energy stress. In Autophagy, 20, 704-706. doi:10.1080/15548627.2023.2280876. https://pubmed.ncbi.nlm.nih.gov/37937799/