title: Low molecular weight protein tyrosine phosphatase (LMWPTP) upregulation mediates malignant potential in colorectal cancer.
abstract: 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.
authors: Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center Rotterdam, 's Gravendijkwa, Rotterdam, The Netherlands.
authors: Elmer
authors: E
authors: Hoekstra
authors: Department of Gastroenterology and Hepatology, Cancer Genomics Centre Netherlands and Centre for Biomedical Genetics, Leiden University Medical Center, Leiden, The Netherlands.
authors: Liudmila L
authors: LL
authors: Kodach
authors: Department of Surgery, Section Surgical Oncology, Laboratory Experimental Surgical Oncology, Erasmus MC, University Medical Center Rotterdam, 's Gravendijkwal, Rotterdam, The Netherlands.
authors: Asha M
authors: AM
authors: Das
authors: Department of Biochemistry, Institute of Biology, University of Campinas, Brazil (UNICAMP), Campinas, Sao Paulo, Brazil.
authors: Roberta R
authors: RR
authors: Ruela-de-Sousa
authors: Department of Biochemistry, Institute of Biology, University of Campinas, Brazil (UNICAMP), Campinas, Sao Paulo, Brazil.
authors: Carmen V
authors: CV
authors: Ferreira
authors: Department of Gastroenterology and Hepatology, Cancer Genomics Centre Netherlands and Centre for Biomedical Genetics, Leiden University Medical Center, Leiden, The Netherlands.
authors: James C
authors: JC
authors: Hardwick
authors: Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center Rotterdam, 's Gravendijkwa, Rotterdam, The Netherlands.
authors: C Janneke
authors: CJ
authors: van der Woude
authors: Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center Rotterdam, 's Gravendijkwa, Rotterdam, The Netherlands.
authors: Maikel P
authors: MP
authors: Peppelenbosch
authors: Department of Surgery, Section Surgical Oncology, Laboratory Experimental Surgical Oncology, Erasmus MC, University Medical Center Rotterdam, 's Gravendijkwal, Rotterdam, The Netherlands.
authors: Timo L M
authors: TL
authors: Ten Hagen
authors: Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center Rotterdam, 's Gravendijkwa, Rotterdam, The Netherlands.
authors: Gwenny M
authors: GM
authors: Fuhler
mesh_terms: D002470:Cell Survival; D015179:Colorectal Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D006801:Humans; D008970:Molecular Weight; D009362:Neoplasm Metastasis; D010766:Phosphorylation; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D059467:Transcriptome; D015854:Up-Regulation
chemical_list: D017027:Protein Tyrosine Phosphatases
keywords: colorectal cancer; kinases and phosphatases; metastasis; signal transduction