Armc8, or armadillo-repeat-containing protein 8, belongs to the armadillo-repeat containing protein family. It is involved in diverse cellular functions, especially cell-cell adhesion complexes through multiple molecular interactions. It interacts with specific δ-catenins (plakophilins-1,-2,-3 and p0071) and αE-catenin [1].

Armc8 has been implicated in multiple cancer-related processes. In hepatocellular carcinoma, its higher expression was associated with larger tumor size, multiple tumors, higher pathological grade, and advanced stages. Knocking down Armc8 in HepG2 cells inhibited their invasive ability and upregulated α-catenin, β-catenin, and E-cadherin expression [2]. In colon cancer, Armc8 was highly expressed in tumor cells compared to adjacent normal tissues, and its expression was related to TNM stage, lymph node metastasis, and poor prognosis. Upregulating Armc8 in HT29 cells enhanced invasiveness and migration, while downregulating it in LoVo cells had the opposite effect [3]. In cutaneous squamous cell carcinomas, ARMC8 was identified as a tumor suppressor as knockdown promoted tumorigenic behaviors, while over-expression inhibited tumorigenesis by restraining the Wnt/β-catenin pathway and epithelial-mesenchymal transition [4]. In breast carcinoma, elevated Armc8 expression was found during atypia-to-carcinoma progression and was associated with lymph node metastasis and advanced TNM stages [5]. In gastric cancer, miR-455-3p inhibited cancer progression by targeting ARMC8 and repressing the Wnt/β-catenin signaling [6]. In ovarian cancer, Armc8 expression was up-regulated, related to disease stages, histology grade, lymph node metastasis, and poor prognosis, and it could promote cell invasion and migration [7]. In osteosarcoma, knockdown of ARMC8 inhibited cell proliferation, invasion, and xenograft tumor growth, and suppressed the epithelial-mesenchymal transition phenotype [8].

In conclusion, Armc8 plays a crucial role in cell-cell adhesion and is significantly involved in the development and progression of multiple cancers, such as hepatocellular, colon, cutaneous squamous cell, breast, gastric, ovarian, and osteosarcoma. These findings from various in vitro and in vivo studies, including some functional loss-of-function experiments, provide insights into its functions and potential as a diagnostic and therapeutic target for these cancers.

References:

1. Gul, Ismail Sahin, Hulpiau, Paco, Sanders, Ellen, van Roy, Frans, van Hengel, Jolanda. 2019. Armc8 is an evolutionarily conserved armadillo protein involved in cell-cell adhesion complexes through multiple molecular interactions. In Bioscience reports, 39, . doi:10.1042/BSR20180604. https://pubmed.ncbi.nlm.nih.gov/30482882/

2. Zhao, Yang, Peng, Songlin, Jia, Changjun, Xu, Yongqing, Dai, Chaoliu. 2016. Armc8 regulates the invasive ability of hepatocellular carcinoma through E-cadherin/catenin complex. In Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine, 37, 11219-24. doi:10.1007/s13277-016-5006-1. https://pubmed.ncbi.nlm.nih.gov/26944057/

3. Jiang, Guiyang, Zhang, Yong, Zhang, Xiupeng, Yu, Juanhan, Wang, Enhua. 2015. ARMc8 indicates aggressive colon cancers and promotes invasiveness and migration of colon cancer cells. In Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine, 36, 9005-13. doi:10.1007/s13277-015-3664-z. https://pubmed.ncbi.nlm.nih.gov/26081621/

4. Li, Xiangzhi, Zhang, Chen, Yuan, Yawen, Zhen, Peilin, Zhou, Meijuan. 2021. Downregulation of ARMC8 promotes tumorigenesis through activating Wnt/β-catenin pathway and EMT in cutaneous squamous cell carcinomas. In Journal of dermatological science, 102, 184-192. doi:10.1016/j.jdermsci.2021.05.002. https://pubmed.ncbi.nlm.nih.gov/34016486/

5. Fan, Chuifeng, Zhao, Yang, Mao, Xiaoyun, Luan, Lan, Wang, Enhua. 2014. Armc8 expression was elevated during atypia-to-carcinoma progression and associated with cancer development of breast carcinoma. In Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine, 35, 11337-43. doi:10.1007/s13277-014-2473-0. https://pubmed.ncbi.nlm.nih.gov/25119601/

6. Zhan, Ting, Chen, Mengge, Liu, Weijie, Tian, Xia, Huang, Xiaodong. 2023. MiR-455-3p inhibits gastric cancer progression by repressing Wnt/β-catenin signaling through binding to ARMC8. In BMC medical genomics, 16, 155. doi:10.1186/s12920-023-01583-y. https://pubmed.ncbi.nlm.nih.gov/37400847/

7. Jiang, Guiyang, Yang, Dalei, Wang, Liang, Wang, Enhua, Zhang, Yong. 2015. A novel biomarker ARMc8 promotes the malignant progression of ovarian cancer. In Human pathology, 46, 1471-9. doi:10.1016/j.humpath.2015.06.004. https://pubmed.ncbi.nlm.nih.gov/26232863/

8. Jiang, Feng, Shi, Yan, Lu, Hong, Li, Guojun. . Armadillo Repeat-Containing Protein 8 (ARMC8) Silencing Inhibits Proliferation and Invasion in Osteosarcoma Cells. In Oncology research, 24, 381-389. doi:10.3727/096504016X14685034103392. https://pubmed.ncbi.nlm.nih.gov/27712595/