Arpc2-KO Mouse

Arpc2, Actin-related protein 2/3 complex subunit 2, is a crucial actin-binding component. It is involved in regulating actin polymerization, mediating the formation of branched actin networks and contacting the mother actin filament. The actin pathway is vital for various biological processes, and Arpc2's role in this pathway is of great biological importance. Genetic models can be valuable for studying its functions [1-10].

In cancer research, ARPC2 has been shown to promote the proliferation, migration, and invasion of cancer cells. In breast cancer, its expression is higher in cancerous tissues, associated with tumor stage and nodal metastasis, and promotes epithelial-mesenchymal transition (EMT) by upregulating related proteins and activating the TGF-β pathway [1]. In hepatocellular carcinoma, its overexpression promotes cell proliferation, migration, and invasion, and is significantly correlated with worse prognosis and higher clinicopathological stage [2]. In gastric cancer, ARPC2 promotes cell proliferation and invasion, and its high expression is associated with large tumor size, lymph node invasion, and high tumor stage [5]. Inhibition of ARPC2 using drugs like benproperine and its stereoisomer S-Benproperine, as well as pimozide, suppresses cancer cell migration and tumor metastasis, suggesting ARPC2 is a potential anti-metastatic target [4,6,7]. In insects, knockdown of Arpc2 in Tribolium castaneum affects metamorphosis and reproduction by integrating ecdysone and juvenile hormone metabolism [3]. In Megalobrama amblycephala, Arpc2 is involved in the CDC42-WASF2-ARPC2 signaling axis which enhances macrophage phagocytosis [8].

In conclusion, Arpc2 is essential for regulating actin polymerization and has significant implications in multiple biological processes. Its role in cancer progression, as revealed through various functional studies including those using potential inhibitor-based models, makes it a promising target for anti-cancer therapy. Additionally, its involvement in insect development and fish immune response shows its broad-reaching biological importance across different species.

References:

1. Cheng, Zhongle, Wei, Wei, Wu, Zhengshen, Han, Yinli, Wu, Qiang. 2019. ARPC2 promotes breast cancer proliferation and metastasis. In Oncology reports, 41, 3189-3200. doi:10.3892/or.2019.7113. https://pubmed.ncbi.nlm.nih.gov/31002363/

2. Huang, Shenglan, Dong, Cairong, Li, Dan, Xu, Yongkang, Wu, Jianbing. 2022. ARPC2: A Pan-Cancer Prognostic and Immunological Biomarker That Promotes Hepatocellular Carcinoma Cell Proliferation and Invasion. In Frontiers in cell and developmental biology, 10, 896080. doi:10.3389/fcell.2022.896080. https://pubmed.ncbi.nlm.nih.gov/35733852/

3. Ge, Runting, Zhang, Ling, Yang, Yanhua, Chen, Keping, Li, Chengjun. 2024. Arpc2 integrates ecdysone and juvenile hormone metabolism to influence metamorphosis and reproduction in Tribolium castaneum. In Pest management science, 80, 3734-3742. doi:10.1002/ps.8076. https://pubmed.ncbi.nlm.nih.gov/38477435/

4. Yoon, Yae Jin, Han, Young-Min, Choi, Jiyeon, Han, Dong Cho, Kwon, Byoung-Mog. 2019. Benproperine, an ARPC2 inhibitor, suppresses cancer cell migration and tumor metastasis. In Biochemical pharmacology, 163, 46-59. doi:10.1016/j.bcp.2019.01.017. https://pubmed.ncbi.nlm.nih.gov/30710516/

5. Zhang, Jun, Liu, Yi, Yu, Chang-Jun, Ding, Rui, Wang, Hong. 2017. Role of ARPC2 in Human Gastric Cancer. In Mediators of inflammation, 2017, 5432818. doi:10.1155/2017/5432818. https://pubmed.ncbi.nlm.nih.gov/28694563/

6. Jang, Hyun-Jin, Yoon, Yae Jin, Choi, Jiyeon, Han, Dong Cho, Kwon, Byoung-Mog. 2022. S-Benproperine, an Active Stereoisomer of Benproperine, Suppresses Cancer Migration and Tumor Metastasis by Targeting ARPC2. In Pharmaceuticals (Basel, Switzerland), 15, . doi:10.3390/ph15121462. https://pubmed.ncbi.nlm.nih.gov/36558913/

7. Choi, Jiyeon, Lee, Yu-Jin, Yoon, Yae Jin, Cho Han, Dong, Kwon, Byoung-Mog. 2019. Pimozide suppresses cancer cell migration and tumor metastasis through binding to ARPC2, a subunit of the Arp2/3 complex. In Cancer science, 110, 3788-3801. doi:10.1111/cas.14205. https://pubmed.ncbi.nlm.nih.gov/31571309/

8. Cui, Hujun, Liu, Yunlong, Zheng, Yancui, Chen, Xiangning, Ding, Zhujin. 2023. Intelectin enhances the phagocytosis of macrophages via CDC42-WASF2-ARPC2 signaling axis in Megalobrama amblycephala. In International journal of biological macromolecules, 236, 124027. doi:10.1016/j.ijbiomac.2023.124027. https://pubmed.ncbi.nlm.nih.gov/36907302/