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| 3 October 2002, Volume 21, Number 44, Pages 6740-6750 |
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| Original Paper |
| Bile acids stimulate invasion and haptotaxis in human colorectal cancer cells through activation of multiple oncogenic signaling pathways |
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| P R Debruyne1, E A Bruyneel1, I-M Karaguni2, Xd Li1, G Flatau3, O Müller2, A Zimber4, C Gespach4 and M M Mareel1 |
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1Laboratory of Experimental Cancerology, Department of Radiotherapy and Nuclear Medicine, Ghent University Hospital, B-9000 Ghent, Belgium
2Max-Planck-Institut für molekulare Physiologie, 44227 Dortmund, Germany
3INSERM U 452, Biologie Cellulaire et Moléculaire des Microorganismes Pathogènes et de leurs Toxines, UFR de Médecine, 06107 Nice Cedex, France
4INSERM U482, Signal Transduction and Cellular Functions in Diabetes and Digestive Cancers, Hôpital Saint-Antoine, 75571 Paris Cedex 12, France
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Correspondence to: M Mareel, Laboratory of Experimental Cancerology, Department of Radiotherapy and Nuclear Medicine, Ghent University Hospital (1P7), De Pintelaan 185, B-9000 Ghent, Belgium; E-mail: marc.mareel@rug.ac.be |
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| Abstract |
| Bile acids are implicated in colorectal carcinogenesis as evidenced by epidemiological and experimental studies. We examined whether bile acids stimulate cellular invasion of human colorectal and dog kidney epithelial cells at different stages of tumor progression. Colon PC/AA/C1, PCmsrc, and HCT-8/E11 cells and kidney MDCKT23 cells were seeded on top of collagen type I gels and invasive cells were counted after 24 h incubation. Activation of the Rac1 and RhoA small GTPases was investigated by pull-down assays. Haptotaxis was analysed with modified Boyden chambers. Lithocholic acid, chenodeoxycholic acid, cholic acid and deoxycholic acid stimulated cellular invasion of SRC- and RhoA-transformed PCmsrc and MDCKT23-RhoAV14 cells, and of HCT-8/E11 cells originating from a sporadic tumor, but were ineffective in premalignant PC/AA/C1 and MDCKT23 cells. Bile acid-stimulated invasion occurred through stimulation of haptotaxis and was dependent on the RhoA/Rho-kinase pathway and signaling cascades using protein kinase C, mitogen-activated protein kinase, and cyclooxygenase-2. Accordingly, BA-induced invasion was associated with activation of the Rac1 and RhoA GTPases and expression of the farnesoid X receptor. We conclude that bile acids stimulate invasion and haptotaxis in colorectal cancer cells via several cancer invasion signaling pathways. Oncogene (2002) 21, 6740-6750. doi:10.1038/sj.onc.1205729 |
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| Keywords |
| bile acids; invasion; colorectal cancer |
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| Received 10 March 2002; revised 16 May 2002; accepted 7 June 2002 |
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| 3 October 2002, Volume 21, Number 44, Pages 6740-6750 |
| Table of contents Previous Abstract Next Full text PDF |
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