Fam135b-KO Mouse

Fam135b, also known as sequence similarity 135 family member B, is significantly associated with cancer-related biological processes. It plays a crucial role in the DNA damage response (DDR) by sustaining the reservoir of Tip60-ATM assembly, which is vital for maintaining genomic integrity. It also participates in regulating alternative splicing related to DNA repair in colorectal cancer, and is involved in signaling pathways like PI3K/Akt/mTOR and Wnt/β-catenin in esophageal squamous cell carcinoma (ESCC) [1,2,3,4].

In ESCC, Fam135B transgenic mouse models have shown that high expression of Fam135B correlates with poorer clinical prognosis. These mice bore heavier tumor burden and had a shorter lifespan after 4-nitroquinoline 1-oxide treatment compared to wild-type mice. Additionally, in vitro studies, such as silencing Fam135B in ESCC cells, revealed its role in enhancing radiosensitivity, likely by regulating the PI3K/Akt/mTOR signaling pathway [3,5].

In conclusion, Fam135b is a key regulator in cancer-related biological processes. Model-based research, especially using transgenic and gene-manipulation mouse models, has provided valuable insights into its role in DNA damage response, cancer cell proliferation, metastasis, and response to chemotherapy and radiotherapy, mainly in colorectal and esophageal cancers. This understanding may potentially contribute to the development of new cancer treatment strategies targeting Fam135b.

References:

1. Zhang, Kai, Wu, Qingnan, Liu, Wenzhong, Zhang, Weimin, Zhan, Qimin. . FAM135B sustains the reservoir of Tip60-ATM assembly to promote DNA damage response. In Clinical and translational medicine, 12, e945. doi:10.1002/ctm2.945. https://pubmed.ncbi.nlm.nih.gov/35979619/

2. Lin, Wanmei, Xu, Lijun, Li, Yaoying, Li, Junze, Zhao, Liang. 2024. Aberrant FAM135B attenuates the efficacy of chemotherapy in colorectal cancer by modulating SRSF1-mediated alternative splicing. In Oncogene, 43, 3532-3544. doi:10.1038/s41388-024-03189-9. https://pubmed.ncbi.nlm.nih.gov/39397154/

3. Bi, Liangwen, Wang, Haijing, Tian, Ye. 2020. Silencing FAM135B enhances radiosensitivity of esophageal carcinoma cell. In Gene, 772, 145358. doi:10.1016/j.gene.2020.145358. https://pubmed.ncbi.nlm.nih.gov/33340561/

4. Zhang, Tong-Tong, Yi, Wei, Dong, De-Zuo, Zhang, Yu, Du, Feng. 2024. METTL3-mediated upregulation of FAM135B promotes EMT of esophageal squamous cell carcinoma via regulating the Wnt/β-catenin pathway. In American journal of physiology. Cell physiology, 327, C329-C340. doi:10.1152/ajpcell.00529.2023. https://pubmed.ncbi.nlm.nih.gov/38881420/

5. Dong, Dezuo, Zhang, Weimin, Xiao, Wenchang, Wang, Weihu, Zhan, Qimin. 2020. A GRN Autocrine-Dependent FAM135B/AKT/mTOR Feedforward Loop Promotes Esophageal Squamous Cell Carcinoma Progression. In Cancer research, 81, 910-922. doi:10.1158/0008-5472.CAN-20-0912. https://pubmed.ncbi.nlm.nih.gov/33323378/