Universität zu Köln

Hinrichsen, Inga, Ernst, Benjamin Philipp, Nuber, Franziska, Passmann, Sandra, Schaefer, Dieter, Steinke, Verena, Friedrichs, Nicolaus, Plotz, Guido, Zeuzem, Stefan and Brieger, Angela (2014). Reduced migration of MLH1 deficient colon cancer cells depends on SPTAN1. Mol. Cancer, 13. LONDON: BIOMED CENTRAL LTD. ISSN 1476-4598

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Abstract

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 all (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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Hinrichsen, Inga UNSPECIFIED UNSPECIFIED UNSPECIFIED Ernst, Benjamin Philipp UNSPECIFIED UNSPECIFIED UNSPECIFIED Nuber, Franziska UNSPECIFIED UNSPECIFIED UNSPECIFIED Passmann, Sandra UNSPECIFIED UNSPECIFIED UNSPECIFIED Schaefer, Dieter UNSPECIFIED UNSPECIFIED UNSPECIFIED Steinke, Verena UNSPECIFIED UNSPECIFIED UNSPECIFIED Friedrichs, Nicolaus UNSPECIFIED UNSPECIFIED UNSPECIFIED Plotz, Guido UNSPECIFIED UNSPECIFIED UNSPECIFIED Zeuzem, Stefan UNSPECIFIED UNSPECIFIED UNSPECIFIED Brieger, Angela UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-448267
DOI:	10.1186/1476-4598-13-11
Journal or Publication Title:	Mol. Cancer
Volume:	13
Date:	2014
Publisher:	BIOMED CENTRAL LTD
Place of Publication:	LONDON
ISSN:	1476-4598
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language MISMATCH REPAIR GENES; COLORECTAL-CANCER; MICROSATELLITE INSTABILITY; FUNCTIONAL-ANALYSIS; MUTL-ALPHA; EXPRESSION; SPECTRIN; HMLH1; MUTATIONS; TUMORS Multiple languages Biochemistry & Molecular Biology; Oncology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/44826