Eps8, also known as Epidermal growth factor receptor pathway substrate 8, was initially identified as a substrate for the kinase activity of the epidermal growth factor receptor (EGFR). It has a domain structure typical of a signaling molecule, containing a putative N-terminal PTB domain, a central SH3 domain, and a C-terminal "effector region". Eps8 is involved in EGFR signaling through Rac, which leads to actin cytoskeletal remodeling, and also in endocytosis through Rab5. It participates in cell mitosis, differentiation, and is related to multiple signaling pathways crucial for normal cell functions [1,2].

Numerous studies have shown that Eps8 is overexpressed in most malignant tumours. Loss-of-function experiments in cancer cells, such as knockdown of Eps8 in non-small-cell lung carcinoma (NSCLC), multiple myeloma (MM), and glioblastoma cells, demonstrated its role in promoting tumour proliferation, invasion, metastasis, and drug resistance. For example, in NSCLC, Eps8 knockdown inhibited cell growth, induced cell-cycle arrest, and increased cisplatin therapeutic effects by interfering with DNA damage repair mechanisms [2,3,4,5]. In MM, Eps8 knockdown abrogated cell survival, migration, and invasion, and overcame drug resistance [5].

In conclusion, Eps8 is a key molecule involved in normal cell signaling, especially related to EGFR-mediated pathways and actin cytoskeletal remodeling. Its overexpression in various cancers and the impact of its knockdown in promoting anti-tumour effects suggest it could be a potential biomarker for cancer diagnosis, prognosis, and a therapeutic target. The functional studies through loss-of-function experiments in cancer cell models have significantly enhanced our understanding of its role in cancer development and progression [2,3,4,5].

References:

1. Di Fiore, Pier Paolo, Scita, Giorgio. . Eps8 in the midst of GTPases. In The international journal of biochemistry & cell biology, 34, 1178-83. doi:. https://pubmed.ncbi.nlm.nih.gov/12127568/

2. Luo, Kaili, Zhang, Lei, Liao, Yuan, Luo, Min, Qing, Chen. 2021. Effects and mechanisms of Eps8 on the biological behaviour of malignant tumours (Review). In Oncology reports, 45, 824-834. doi:10.3892/or.2021.7927. https://pubmed.ncbi.nlm.nih.gov/33432368/

3. Yang, Gang, Lu, Yong-Bin, Guan, Quan-Lin. 2019. EPS8 is a Potential Oncogene in Glioblastoma. In OncoTargets and therapy, 12, 10523-10534. doi:10.2147/OTT.S227739. https://pubmed.ncbi.nlm.nih.gov/31819533/

4. Qiu, Yingqi, Xu, Binyan, Feng, Jianhua, Xie, Xiaoling, Li, Yuhua. 2023. Loss of EPS8 sensitizes non-small-cell lung carcinoma to chemotherapy-induced DNA damage. In Cancer gene therapy, 30, 997-1006. doi:10.1038/s41417-023-00606-1. https://pubmed.ncbi.nlm.nih.gov/36932195/

5. Zhang, Honghao, Zhou, Lijuan, Zhou, Weijun, He, Yanjie, Li, Yuhua. 2019. EPS8-mediated regulation of multiple myeloma cell growth and survival. In American journal of cancer research, 9, 1622-1634. doi:. https://pubmed.ncbi.nlm.nih.gov/31497346/