Title:The Functions of EphA1 Receptor Tyrosine Kinase in Several Tumors
Volume: 30
Issue: 20
Author(s): Yinxin Wu, Zhuoying Du, Jie Mou, Xinyan Qiu, Jinlan Chen, Sanjin Cai, Dongming Ren, Fangxiang Xiao, Gang Zhou*Chengfu Yuan*
Affiliation:
- College of Traditional Chinese Medicine, China Three Gorges University, Yichang, 443002, P.R. China
- Yichang
Hospital of Traditional Chinese Medicine, Yichang, 443002, P.R. China
- Third-Grade Pharmacological Laboratory on Traditional Chinese Medicine, State Administration of Traditional Chinese Medicine, China
Three Gorges University, Yichang 443002, P.R. China
- College of Basic Medical Science, China Three Gorges University, Yichang
443002, P.R. China
Keywords:
RTK, EphA1, tumors, hepatocellular carcinoma, biomarkers, diagnosis, angiogenesis.
Abstract:
Background: Eph receptors tyrosine kinase (RTK) were identified in 1987 from hepatocellular carcinoma
cell lines and were the largest known subfamily of RTK. Eph receptors can be divided into two categories,
EphA and EphB, based on their structure and receptor-ligand specificity. EphA can be divided into 10
species (EphA 1-10) and EphB into 6 species (EphB1-6). Similarly, the ligands of Eph receptors are Ephrins.
Ephrins also can be divided into Ephrin A and Ephrin B, of which there are five species(Ephrin-A1-5) and three
species(Ephrin-B1-3). Among the Eph receptors, EphA1 has been the least studied so far. As far as we know,
Eph receptors are involved in multiple pathologies, including cancer progression, tumor angiogenesis, intestinal
environmental stability, the lymph node system, neurological disease, and inhibition of nerve regeneration after
injury. There is a link between EphA1, integrin and ECM- related signal pathways. Ephrin-A1 is a ligand of the
EphA1 receptor. EphA1 and ephrin-A1 functions are related to tumor angiogenesis. EphA1 and ephrin-A1 also
play roles in gynecological diseases. Ephrin-A1 and EphA1 receptors regulate the follicular formation, ovulation,
embryo transport, implantation and placental formation, which are of great significance for the occurrence
of gynecological tumor diseases. EphA1 has been identified as an oncoprotein in various tumors and has been
associated with the prognosis of various tumors in recent years. EphA1 is considered a driver gene in tumor genomics.
There are significant differences in EphA1 expression levels in different types of normal tissues and tumors
and even in different stages of tumor development, suggesting its functional diversity. Changes at the
gene level in cell biology are often used as biological indicators of cancer, known as biomarkers, which can be
used to provide diagnostic or prognostic information and are valuable for improving the detection, monitoring
and treatment of tumors. However, few prognostic markers can selectively predict clinically significant tumors
with poor prognosis. These malignancies are more likely to progress and lead to death, requiring more aggressive
treatment. Currently available treatments for advanced cancer are often ineffective, and treatment options
are mainly palliative. Therefore, early identification and treatment of those at risk of developing malignant tumors
are crucial. Although pieces of evidence have shown the role of EphA1 in tumorigenesis and development,
its specific mechanism is still unknown to a great extent.
Objective: This review reveals the changes and roles of EphA1 in many tumors and cancers. The change of
EphA1 expression can be used as a biological marker of cancer, which is valuable for improving tumor detection,
monitoring and treatment and can be applied to imaging. Studies have shown that structural modification
of EphA1 could make it an effective new drug. EphA1 is unique in that it can be considered a prognostic marker
in many tumors and is of important meaning for clinical diagnosis and operative treatment. At the same time,
the study of the specific mechanism of EphA1 in tumors can provide a new way for targeted therapy.
Methods: Relevant studies were retrieved and collected through the PubMed system. After determining EphA1
as the research object, by analyzing research articles on EphA1 in the PubMed system in recent 10 years, we
found that EphA1 was closely connected with the occurrence and development of tumors and further determined
the references according to the influencing factors for review and analysis.
Results: EphA1 has been identified as a cancer protein in various tumors, such as hepatocellular carcinoma, nasopharyngeal
carcinoma, ovarian cancer, gastric cancer, colorectal cancer, clear cell renal cell carcinoma,
esophageal squamous cell carcinoma, breast cancer, prostate cancer and uveal melanoma. EphA1 is abnormally
expressed in these tumor cells, which mainly plays a role in cancer progression, tumor angiogenesis, intestinal
environmental stability, the lymph node system, nervous system diseases and gynecological diseases. In a narrow
sense, EphA1 is especially effective in breast cancer in terms of gynecological diseases. However, the specific
mechanism of EphA1 leading to the change of cancer cells in some tumors is not clear, which needs further
research and exploration.
Conclusion: RTK EphA1 can be used as a biomarker for tumor diagnosis (especially a prognostic marker), an
indispensable therapeutic target for new anti-tumor therapies, and a novel anti-tumor drug.
