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Updated: Jun 4, 2026
11:48
Detection of Alternative Splicing During Epithelial-Mesenchymal Transition
Published on: October 9, 2014
An N-terminal truncated carboxypeptidase E splice isoform induces tumor growth and is a biomarker for predicting
Terence K Lee1, Saravana R K Murthy, Niamh X Cawley
1Department of Surgery, University of Hong Kong, Pokfulam, Hong Kong, China.
The Journal of Clinical Investigation
|February 3, 2011
Summary
A newly identified protein fragment, carboxypeptidase E-delta N (CPE-ΔN), drives cancer metastasis. Measuring CPE-ΔN levels can predict metastasis and recurrence in liver and neuroendocrine tumors.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Metastasis is a primary cause of cancer mortality, yet its mechanisms are not fully understood.
- Accurate biomarkers for predicting metastasis are scarce, limiting effective therapeutic guidance.
Purpose of the Study:
- To investigate the role of alternatively spliced carboxypeptidase E (CPE) variants in cancer metastasis.
- To identify novel biomarkers for predicting metastasis and recurrence in specific cancer types.
Main Methods:
- Analysis of CPE gene splicing in human tumor samples and cell lines.
- Investigating the function of the N-terminal truncated CPE protein (CPE-ΔN) in hepatocellular carcinoma (HCC) cells.
- Assessing the correlation between CPE-ΔN levels and metastatic potential in HCC and pheochromocytomas/paragangliomas (PHEOs/PGLs) patient samples.
Main Results:
- Elevated CPE-ΔN mRNA was detected in metastatic colon, breast, and HCC cell lines.
- In HCC, CPE-ΔN translocated to the nucleus, interacted with histone deacetylase 1/2, and upregulated neural precursor cell expressed, developmentally downregulated gene 9 (Nedd9), enhancing proliferation and invasion.
- CPE-ΔN mRNA levels accurately predicted intrahepatic metastasis in HCC patients and metastasis/recurrence in PHEO/PGL patients, independent of cancer stage.
Conclusions:
- Alternative splicing of CPE generates a metastasis-driving protein, CPE-ΔN.
- CPE-ΔN functions by upregulating Nedd9 expression, promoting tumor cell proliferation and invasion.
- CPE-ΔN serves as a potent predictive biomarker for metastasis and recurrence in HCC and PHEO/PGL.
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