Reduced migration of MLH1 deficient colon cancer cells depends on SPTAN1
| Autor: | Dieter Schäfer, Verena Steinke, Stefan Zeuzem, Sandra Passmann, Franziska Nuber, Inga Hinrichsen, Angela Brieger, Guido Plotz, Benjamin Philipp Ernst, Nicolaus Friedrichs |
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| Rok vydání: | 2014 |
| Předmět: |
Adult
Male congenital hereditary and neonatal diseases and abnormalities Cancer Research Colorectal cancer DNA mismatch repair Blotting Western Biology Transfection MLH1 Metastasis Cell Movement Cell Line Tumor medicine Humans Immunoprecipitation Neoplasm Invasiveness Spectrin ddc:610 RNA Small Interfering Nuclear protein neoplasms Adaptor Proteins Signal Transducing Aged Aged 80 and over Cellular mobility Reverse Transcriptase Polymerase Chain Reaction Research Microfilament Proteins Nuclear Proteins nutritional and metabolic diseases Middle Aged SPTAN1 medicine.disease Immunohistochemistry digestive system diseases Cytoskeletal proteins Oncology Gene Knockdown Techniques Colonic Neoplasms Cancer research Molecular Medicine Female Carrier Proteins MutL Protein Homolog 1 |
| Zdroj: | Molecular Cancer |
| ISSN: | 1476-4598 |
| DOI: | 10.1186/1476-4598-13-11 |
| Popis: | Introduction Defects in the DNA mismatch repair (MMR) protein MLH1 are frequently observed in sporadic and hereditary colorectal cancers (CRC). Affected tumors generate much less metastatic potential than the MLH1 proficient forms. Although MLH1 has been shown to be not only involved in postreplicative MMR but also in several MMR independent processes like cytoskeletal organization, the connection between MLH1 and metastasis remains unclear. We recently identified non-erythroid spectrin αII (SPTAN1), a scaffolding protein involved in cell adhesion and motility, to interact with MLH1. In the current study, the interaction of MLH1 and SPTAN1 and its potential consequences for CRC metastasis was evaluated. Methods Nine cancer cell lines as well as fresh and paraffin embedded colon cancer tissue from 12 patients were used in gene expression studies of SPTAN1 and MLH1. Co-expression of SPTAN1 and MLH1 was analyzed by siRNA knock down of MLH1 in HeLa, HEK293, MLH1 positive HCT116, SW480 and LoVo cells. Effects on cellular motility were determined in MLH1 deficient HCT116 and MLH1 deficient HEK293T compared to their MLH1 proficient sister cells, respectively. Results MLH1 deficiency is clearly associated with SPTAN1 reduction. Moreover, siRNA knock down of MLH1 decreased the mRNA level of SPTAN1 in HeLa, HEK293 as well as in MLH1 positive HCT116 cells, which indicates a co-expression of SPTAN1 by MLH1. In addition, cellular motility of MLH1 deficient HCT116 and MLH1 deficient HEK293T cells was impaired compared to the MLH1 proficient sister clones. Consequently, overexpression of SPTAN1 increased migration of MLH1 deficient cells while knock down of SPTAN1 decreased cellular mobility of MLH1 proficient cells, indicating SPTAN1-dependent migration ability. Conclusions These data suggest that SPTAN1 levels decreased in concordance with MLH1 reduction and impaired cellular mobility in MLH1 deficient colon cancer cells. Therefore, aggressiveness of MLH1-positive CRC might be related to SPTAN1. |
| Databáze: | OpenAIRE |
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