Calcium-binding protein S100P is a new target gene of MACC1, drives colorectal cancer metastasis and serves as a prognostic biomarker.
Autor: | Schmid F; Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.; Experimental and Clinical Research Center of the Charité - Universitätsmedizin Berlin and the Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association, Robert-Rössle-Straße 10, 13125, Berlin, Germany., Dahlmann M; Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.; Experimental and Clinical Research Center of the Charité - Universitätsmedizin Berlin and the Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association, Robert-Rössle-Straße 10, 13125, Berlin, Germany.; German Cancer Consortium (DKTK), Im Neuenheimer Feld 280, 69120, Heidelberg, Germany., Röhrich H; Experimental and Clinical Research Center of the Charité - Universitätsmedizin Berlin and the Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association, Robert-Rössle-Straße 10, 13125, Berlin, Germany., Kobelt D; Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.; Experimental and Clinical Research Center of the Charité - Universitätsmedizin Berlin and the Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association, Robert-Rössle-Straße 10, 13125, Berlin, Germany., Hoffmann J; Experimental Pharmacology and Oncology Berlin-Buch GmbH, Robert-Rössle-Straße 10, 13125, Berlin, Germany., Burock S; Charité Comprehensive Cancer Center, Invalidenstraße 80, 10117, Berlin, Germany., Walther W; Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.; Experimental and Clinical Research Center of the Charité - Universitätsmedizin Berlin and the Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association, Robert-Rössle-Straße 10, 13125, Berlin, Germany., Stein U; Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany. ustein@mdc-berlin.de.; Experimental and Clinical Research Center of the Charité - Universitätsmedizin Berlin and the Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association, Robert-Rössle-Straße 10, 13125, Berlin, Germany. ustein@mdc-berlin.de.; German Cancer Consortium (DKTK), Im Neuenheimer Feld 280, 69120, Heidelberg, Germany. ustein@mdc-berlin.de. |
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Jazyk: | angličtina |
Zdroj: | British journal of cancer [Br J Cancer] 2022 Sep; Vol. 127 (4), pp. 675-685. Date of Electronic Publication: 2022 May 21. |
DOI: | 10.1038/s41416-022-01833-3 |
Abstrakt: | Background: The metastasis inducing gene MACC1 is a prognostic and predictive biomarker for metastasis in several cancers. Its mechanism of inducing metastasis includes the transcriptional control of other cancer-related target genes. Here, we investigate the interplay with the metastasis driver S100P in CRC progression. Methods: MACC1-dependent S100P expression was analysed by qRT-PCR. The binding of MACC1 to the S100P promoter was determined by ChIP. Alterations in cell proliferation and motility were determined by functional in vitro assays. In vivo metastasis after intrasplenic transplantation was assessed by bioluminescence imaging and evaluation of tumour growth and liver metastasis. The prognostic value of S100P was determined in CRC patients by ROC-based Kaplan-Meier analyses. Results: Expression of S100P and MACC1 correlated positively in CRC cells and colorectal tumours. MACC1 was found binding to the S100P promoter and induces its expression. The overexpression of S100P increased proliferation, migration and invasion in vitro and significantly induced liver metastasis in vivo. S100P expression was significantly elevated in metachronously metastasising CRC and was associated with shorter metastasis-free survival. Conclusions: We identified S100P as a transcriptional target gene of MACC1. Expression of S100P increases the metastatic potential of CRC cells in vitro and in vivo, and serves as a prognostic biomarker for metastasis-free survival of CRC patients, emphasising novel therapeutic interventions targeting S100P. (© 2022. The Author(s).) |
Databáze: | MEDLINE |
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