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Published on: July 20, 2019
NEDD4L in human tumors: regulatory mechanisms and dual effects on anti-tumor and pro-tumor
Meng Zhang1, Zhenyong Zhang1, Xin Tian1
1Department of Oncology, Shengjing Hospital of China Medical University, Shenyang, China.
Abstract:
Tumorigenesis and tumor development are closely related to the abnormal regulation of ubiquitination. Neural precursor cell expressed developmentally downregulated 4-like (NEDD4L), an E3 ubiquitin ligase critical to the ubiquitination process, plays key roles in the regulation of cancer stem cells, as well as tumor cell functions, including cell proliferation, apoptosis, cell cycle regulation, migration, invasion, epithelial-mesenchymal transition (EMT), and tumor drug resistance, by controlling subsequent protein degradation through ubiquitination. NEDD4L primarily functions as a tumor suppressor in several tumors but also plays an oncogenic role in certain tumors. In this review, we comprehensively summarize the relevant signaling pathways of NEDD4L in tumors, the regulatory mechanisms of its upstream regulatory molecules and downstream substrates, and the resulting functional alterations. Overall, therapeutic strategies targeting NEDD4L to treat cancer may be feasible.
Insights
Neural precursor cell expressed developmentally downregulated 4-like (NEDD4L) is crucial in tumor development by regulating ubiquitination. Targeting NEDD4L offers potential cancer therapeutic strategies.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Tumorigenesis is linked to aberrant ubiquitination.
- Neural precursor cell expressed developmentally downregulated 4-like (NEDD4L) is an E3 ubiquitin ligase involved in protein degradation.
- NEDD4L's role in cancer is complex, acting as both a tumor suppressor and oncogene.
Purpose of the Study:
- To comprehensively review NEDD4L's signaling pathways in tumors.
- To elucidate upstream regulatory mechanisms and downstream substrates of NEDD4L.
- To understand NEDD4L's functional alterations in cancer development.
Main Methods:
- Literature review of studies on NEDD4L in tumorigenesis.
- Analysis of signaling pathways regulated by NEDD4L.
- Examination of NEDD4L's role in cancer stem cell regulation and tumor cell functions.
Main Results:
- NEDD4L influences cell proliferation, apoptosis, cell cycle, migration, invasion, EMT, and drug resistance.
- NEDD4L acts as a tumor suppressor in some cancers and an oncogene in others.
- Upstream and downstream regulatory networks of NEDD4L in cancer are identified.
Conclusions:
- NEDD4L plays multifaceted roles in cancer progression.
- Understanding NEDD4L's regulatory mechanisms is key to cancer therapy.
- Targeting NEDD4L presents a feasible therapeutic strategy for cancer treatment.
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