Cmtm8, short for chemokine-like factor-like MARVEL transmembrane domain-containing family member 8, has been shown to have tumor-inhibiting activities [7]. It may be involved in regulating multiple signaling pathways such as the calcium signaling pathway, cell adhesion molecules, and cytokine-cytokine receptor interaction [1]. It is widely expressed in normal human tissues but frequently downregulated in multiple solid tumors, suggesting its potential role as a tumor suppressor [4].

In gastric cancer, lower Cmtm8 protein expression is related to poor prognosis, metastasis, and it is an independent protective factor for overall survival [1]. In pancreatic cancer, Cmtm8 serves as a key mediator of lysophosphatidic acid-induced invasiveness through interaction with LPA1 and activation of β-catenin signaling [2]. In human mesenchymal stem cells, knockdown of Cmtm8 decreases proliferation and migration but increases osteogenic differentiation, with Cmtm8 promoting these processes via the EGFR/ERK1/2 pathway [3]. In bladder cancer, overexpression of Cmtm8 reduces malignant cell growth, migration, and invasion both in vitro and in vivo [5]. Polymorphisms in Cmtm8 are associated with increased lung cancer risk [6]. In triple-negative breast cancer, miR-582-5p promotes invasion and metastasis by antagonizing Cmtm8 [8]. In colon cancer, Cmtm8 is identified as an EMT-immune-related prognostic biomarker [9].

In summary, Cmtm8 plays crucial roles in tumorigenesis and development across multiple cancer types, often acting as a suppressor of cancer cell growth, migration, and invasion. Its involvement in various signaling pathways and association with disease prognosis highlight its significance in understanding cancer biology and potentially developing novel therapeutic strategies. The studies using different models, though not specifically KO/CKO mouse models in the provided references, still reveal important functions of Cmtm8 in disease conditions.

References:

1. Yan, Meng, Zhu, Xiaonian, Qiao, Haizhi, Xie, Wenjie, Cai, Jianhui. 2021. Downregulated CMTM8 Correlates with Poor Prognosis in Gastric Cancer Patients. In DNA and cell biology, 40, 791-797. doi:10.1089/dna.2021.0110. https://pubmed.ncbi.nlm.nih.gov/33978454/

2. Shi, Weidong, Zhang, Chenyue, Ning, Zhouyu, Chen, Zhen, Meng, Zhiqiang. . CMTM8 as an LPA1-associated partner mediates lysophosphatidic acid-induced pancreatic cancer metastasis. In Annals of translational medicine, 9, 42. doi:10.21037/atm-20-1013. https://pubmed.ncbi.nlm.nih.gov/33553335/

3. H'ng, Chee Ho, Camp, Esther, Anderson, Peter J, Zannettino, Andrew C W, Gronthos, Stan. 2020. CMTM8 Is a Suppressor of Human Mesenchymal Stem Cell Osteogenic Differentiation and Promoter of Proliferation Via EGFR Signaling. In Stem cells and development, 29, 823-834. doi:10.1089/scd.2020.0007. https://pubmed.ncbi.nlm.nih.gov/32268840/

4. Zhang, Wenjuan, Qi, Hui, Mo, Xiaoning, Ma, Dalong, Wang, Ying. . CMTM8 is Frequently Downregulated in Multiple Solid Tumors. In Applied immunohistochemistry & molecular morphology : AIMM, 25, 122-128. doi:10.1097/PAI.0000000000000274. https://pubmed.ncbi.nlm.nih.gov/26574634/

5. Gao, Denghui, Hu, Hao, Wang, Ying, Zhou, Chunyan, Xu, Kexin. . CMTM8 inhibits the carcinogenesis and progression of bladder cancer. In Oncology reports, 34, 2853-63. doi:. https://pubmed.ncbi.nlm.nih.gov/26503336/

6. Wu, Jiamin, Sun, Yao, Xiong, Zichao, Liu, Qiufang, Jin, Tianbo. . Influence of CMTM8 polymorphisms on lung cancer susceptibility in the Chinese Han population. In Pharmacogenetics and genomics, 31, 89-95. doi:10.1097/FPC.0000000000000426. https://pubmed.ncbi.nlm.nih.gov/33395025/

7. Gao, Deng-Hui, Hu, Hao, Fang, Zhi-Wei, Xu, Ke-Xin, Wang, Xiao-Feng. . Research Advances in Chemokine-like Factor Super Family Member 8. In Zhongguo yi xue ke xue yuan xue bao. Acta Academiae Medicinae Sinicae, 38, 746-749. doi:10.3881/j.issn.1000-503X.2016.06.021. https://pubmed.ncbi.nlm.nih.gov/28065246/

8. Zeng, Xue, Ma, Xinchi, Guo, Hong, Sun, Shichen, Zhang, Na. . MicroRNA-582-5p promotes triple-negative breast cancer invasion and metastasis by antagonizing CMTM8. In Bioengineered, 12, 10126-10135. doi:10.1080/21655979.2021.2000741. https://pubmed.ncbi.nlm.nih.gov/34978519/

9. Kang, Ning, Xie, Xiaoli, Zhou, Xue, Liu, Ting, Jiang, Huiqing. 2022. Identification and validation of EMT-immune-related prognostic biomarkers CDKN2A, CMTM8 and ILK in colon cancer. In BMC gastroenterology, 22, 190. doi:10.1186/s12876-022-02257-2. https://pubmed.ncbi.nlm.nih.gov/35429970/