Research Overview
Understanding the molecular mechanisms of mitotic control in cancer and exploring therapeutic applications.
- Regulation of cell division by EphA2 signaling
- Role in cancer progression
- Potential as a therapeutic target
Our laboratory investigates the molecular mechanisms of mitotic control and EphA2 signaling using cell biological and molecular biological approaches.
Keywords
Mitotic control / EphA2 / Ephexin4 / RhoG / Cell cycle / Cancer biology
EphA2 and Cell Division
Our research focuses on the role of EphA2 signaling in the regulation of cell division and cancer progression.
Our goal is to elucidate the molecular mechanisms underlying EphA2-mediated cell division regulation and to explore its potential as a therapeutic target in cancer.
EphA2 is a member of the Eph receptor family, the largest family of receptor tyrosine kinases, and plays important roles in regulating cell proliferation and migration during development and tissue formation. Its ligand, ephrin-A1, mediates cell–cell repulsion that guides tissue patterning. Although EphA2 expression is generally low in adult tissues, it is frequently overexpressed in a wide range of cancers, including colorectal, lung, pancreatic, and breast cancers, as well as metastatic melanoma.
In cancer cells, EphA2 can be activated independently of ligand binding, promoting growth, survival, and migration through multiple signaling pathways. Our research has revealed that during cell division, EphA2 Ser897 is phosphorylated through the CDK1–MEK/ERK–RSK signaling cascade. This phosphorylation regulates spindle formation and cortical stiffness via activation of Ephexin4/RhoG. These findings indicate that EphA2 plays important roles not only in cancer progression but also in the regulation of normal cell division.
Moreover, we recently found that EphA2 is upregulated in response to DNA damage and suppresses p53/p21 transcriptional activation. Knockdown of EphA2 induces p21 upregulation under DNA damage conditions. As a result, a subset of cells undergoes mitotic bypass instead of G2 arrest, leading to suppression of cell proliferation. Interestingly, these effects were observed in cervical cancer cell lines but not in colorectal or breast cancer cell lines. These findings suggest that EphA2 signaling plays a previously unrecognized role in determining cell fate after DNA damage and may provide new insights into anti-cancer strategies for certain cancer types.