First published March 18, 2019 - More info
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.
Terence K. Lee, Saravana R.K. Murthy, Niamh X. Cawley, Savita Dhanvantari, Stephen M. Hewitt, Hong Lou, Tracy Lau, Stephanie Ma, Thanh Huynh, Robert A. Wesley, Irene O. Ng, Karel Pacak, Ronnie T. Poon, Y. Peng Loh
Original citation: J Clin Invest. 2011;121(3):880–892. https://doi.org/10.1172/JCI40433
Citation for this retraction: J Clin Invest. 2019;129(4):1804. https://doi.org/10.1172/JCI128836
The Editorial Board has recently been informed that the NIH examined the primary data from pheochromocytoma patients used to construct Table 4. Evidence shows that the data on the pheochromocytoma patients in Table 4 are not reliable. Due to this finding, the JCI is retracting this article.
Niamh X. Cawley, Stephen M. Hewitt, Hong Lou, Thanh Huynh, and Karel Pacak have agreed with the Journal’s decision to retract the paper. Terence K. Lee, Saravana R.K. Murthy, Savita Dhanvantari, Tracy Lau, Stephanie Ma, and Irene O. Ng dissent from the retraction. Ronnie T. Poon and Robert A. Wesley could not be reached, and Y. Peng Loh abstained from commenting.