Low molecular weight protein tyrosine phosphatase (LMWPTP) upregulation mediates malignant potential in colorectal cancer
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Elmer Hoekstra1, Liudmila L. Kodach2, Asha M. Das3, Roberta R. Ruela-de-Sousa4, Carmen V. Ferreira4, James C. Hardwick2, C. Janneke van der Woude1, Maikel P. Peppelenbosch1, Timo L.M. ten Hagen3, Gwenny M. Fuhler1
1Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center Rotterdam, 's Gravendijkwal 230, NL-3015 CE Rotterdam, The Netherlands
2Department of Gastroenterology and Hepatology, Cancer Genomics Centre Netherlands and Centre for Biomedical Genetics, Leiden University Medical Center, Leiden, The Netherlands
3Department of Surgery, Section Surgical Oncology, Laboratory Experimental Surgical Oncology, Erasmus MC, University Medical Center Rotterdam, 's Gravendijkwal 230, NL-3015 CE Rotterdam, The Netherlands
4Department of Biochemistry, Institute of Biology, University of Campinas, Brazil (UNICAMP), Campinas, Sao Paulo, Brazil
Gwenny M. Fuhler, e-mail: firstname.lastname@example.org
Keywords: Colorectal cancer, kinases and phosphatases, signal transduction, metastasis
Received: December 10, 2014 Accepted: January 26, 2015 Published: March 14, 2015
Phosphatases have long been regarded as tumor suppressors, however there is emerging evidence for a tumor initiating role for some phosphatases in several forms of cancer. Low Molecular Weight Protein Tyrosine Phosphatase (LMWPTP; acid phosphatase 1 [ACP1]) is an 18 kDa enzyme that influences the phosphorylation of signaling pathway mediators involved in cancer and is thus postulated to be a tumor-promoting enzyme, but neither unequivocal clinical evidence nor convincing mechanistic actions for a role of LMWPTP have been identified. In the present study, we show that LMWPTP expression is not only significantly increased in colorectal cancer (CRC), but also follows a step-wise increase in different levels of dysplasia. Chemical inhibition of LMWPTP significantly reduces CRC growth. Furthermore, downregulation of LMWPTP in CRC leads to a reduced migration ability in both 2D- and 3D-migration assays, and sensitizes tumor cells to the chemotherapeutic agent 5-FU. In conclusion, this study shows that LMWPTP is not only overexpressed in colorectal cancer, but it is correlated with the malignant potential of this cancer, suggesting that this phosphatase may act as a predictive biomaker of CRC stage and represents a rational novel target in the treatment of this disease.
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