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UNC5 dependence receptor family in human cancer: A controllable double-edged sword
Yuyan Zhu1, Yuanyuan Li2, Akira Nakagawara3
1Department of Urology, The First Hospital of China Medical University, Shenyang, China.
Abstract:
UNC5 receptor family (UNC5A-D) have been identified as dependence receptors whose functions depend on the availability of their ligand netrin-1. Through binding to netrin-1, these receptors transmit signals for cell survival, migration and differentiation, and participate in diverse physiological and pathological processes. In the lack of netrin-1, however, these receptors initiate apoptosis-inducing signal. Accumulating evidence reveals that netrin-1 and its receptors play a role in tumorigenesis and tumor progression. The expression of UNC5 receptor family is down-regulated in a variety of human tumors. Expression aberrance of UNC5 receptor family in tumors is caused by diverse mechanisms including genomic, epigenetic, transcriptional and post-transcriptional regulation. Notably, blocking netrin-1 binding to its receptors induces apoptotic cell death in tumor cells. In this review, we describe the characters and roles of UNC5 family members in tumorigenesis and tumor progression, discussing the regulatory mechanisms underlying down-regulation of UNC5 family members as well as recent implications of targeting netrin-1/UNC5 on potential clinical application for cancer treatment.
Insights
The UNC5 receptor family (UNC5A-D) acts as dependence receptors, crucial in cell survival and apoptosis. Their dysregulation in tumors presents a potential therapeutic target for cancer treatment by blocking netrin-1 signaling.
Area of Science:
- Molecular biology
- Cell biology
- Oncology
Background:
- The UNC5 receptor family (UNC5A-D) are dependence receptors activated by netrin-1.
- Netrin-1 binding regulates cell survival, migration, and differentiation.
- Absence of netrin-1 triggers apoptosis via UNC5 receptors.
Purpose of the Study:
- To review the role of UNC5 receptors in tumorigenesis and tumor progression.
- To discuss mechanisms causing UNC5 receptor down-regulation in cancers.
- To explore targeting the netrin-1/UNC5 pathway for cancer therapy.
Main Methods:
- Literature review of studies on UNC5 receptors and netrin-1 in cancer.
- Analysis of regulatory mechanisms (genomic, epigenetic, transcriptional, post-transcriptional) affecting UNC5 expression.
- Evaluation of clinical implications of targeting the netrin-1/UNC5 axis.
Main Results:
- UNC5 receptor family expression is frequently down-regulated in human tumors.
- Dysregulation of UNC5 receptors contributes to tumorigenesis and progression.
- Blocking netrin-1/UNC5 interaction induces tumor cell apoptosis.
Conclusions:
- The netrin-1/UNC5 pathway is implicated in cancer development and progression.
- Understanding UNC5 regulation is key to developing novel cancer treatments.
- Targeting the netrin-1/UNC5 axis shows promise for clinical cancer therapy.
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