An N-terminal truncated carboxypeptidase E splice isoform induces tumor growth and is a biomarker for predicting future metastasis in human cancers
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Post-publication record
- Nature
- Retraction
- Reason
- Investigation by Company/Institution;Unreliable Data;
- Date
- 3/18/2019 0:00
- Flagged by OpenAlex?
- Yes
Source: Retraction Watch, joined by DOI. OpenAlex records retraction as is_retracted, a boolean over a state space with at least four values, so it cannot express an expression of concern, a correction or a reinstatement — it reports them as false, which reads as “fine”.
Abstract
Metastasis is a major cause of mortality in cancer patients. However, the mechanisms governing the metastatic process remain elusive, and few accurate biomarkers exist for predicting whether metastasis will occur, something that would be invaluable for guiding therapy. We report here that the carboxypeptidase E gene (CPE) is alternatively spliced in human tumors to yield an N-terminal truncated protein (CPE-ΔN) that drives metastasis. mRNA encoding CPE-ΔN was found to be elevated in human metastatic colon, breast, and hepatocellular carcinoma (HCC) cell lines. In HCC cells, cytosolic CPE-ΔN was translocated to the nucleus and interacted with histone deacetylase 1/2 to upregulate expression of the gene encoding neural precursor cell expressed, developmentally downregulated gene 9 (Nedd9)--which has been shown to promote melanoma metastasis. Nedd9 upregulation resulted in enhanced in vitro proliferation and invasion. Quantification of mRNA encoding CPE-ΔN in HCC patient samples predicted intrahepatic metastasis with high sensitivity and specificity, independent of cancer stage. Similarly, high CPE-ΔN mRNA copy numbers in resected pheochromocytomas/paragangliomas (PHEOs/PGLs), rare neuroendocrine tumors, accurately predicted future metastasis or recurrence. Thus, CPE-ΔN induces tumor metastasis and should be investigated as a potentially powerful biomarker for predicting future metastasis and recurrence in HCC and PHEO/PGL patients.
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The record
- Venue
- Journal of Clinical Investigation
- Topic
- Protein Degradation and Inhibitors
- Field
- Biochemistry, Genetics and Molecular Biology
- Canadian institutions
- Lawson Health Research Institute
- Funders
- Natural Sciences and Engineering Research Council of CanadaNational Institutes of HealthLawson Health Research Institute
- Keywords
- MetastasisCancer researchCancerBiologyBiomarkerMelanomaDownregulation and upregulationGene knockdownCell cultureGeneGenetics
- Has abstract in OpenAlex
- yes