CCN3: Doctor Jekyll and Mister Hyde.
CCN proteins are key regulators of signaling pathways that are essential for the control of normal life, from birth to death. As such, they make use of their unique mosaic structure to interact with several other regulatory proteins and ligands that control the fate of living cells. The various functions attributed to the CCN proteins may sometimes appear contradictory, but this situation reflects the complexity of the multimolecular scaffolds in which CCN proteins are engaged and the critical impact of the microenvironment that dictates the bioavailability of the elementary building blocks. CCN3 is one of the best examples of a CCN protein showing biological properties which may at first glance appear opposite or contradictory. Indeed, CCN3 acts both as a tumor suppressor and is associated with higher metastatic potential. Furthermore, the physical interaction of CCN3 with VEGF and its potential antiangionenic activity in glioma cells are in apparent contradiction with its proangiogenic activity in rabbit cornea. In this communication, I am revisiting the observations that led us to these apparent contradictions. After pointing out how the methodologies that were employed might have contributed to the confusion, I briefly discuss the dual biological activities of CCN3 in the context of tumor cell engineering and survival prognosis.
Perbal
Bernard
B
Research and Development - L'Oréal USA, 111 Terminal Avenue, Clark, NJ, 07066, USA, bperbal@gmail.com.
Lancet. 2004 Jan 3;363(9402):62-4
14723997
Mol Pathol. 2001 Oct;54(5):293-9
11577170
J Cell Sci. 2006 Dec 1;119(Pt 23):4803-10
17130294
Cell Commun Signal. 2006 Feb 20;4:3
16504021
Blood. 2006 Sep 1;108(5):1716-23
16670264
Gene. 1999 Oct 1;238(2):471-8
10570975
Cancer Res. 2008 Feb 1;68(3):715-23
18245471
Am J Pathol. 1998 Jun;152(6):1563-75
9626060
Clin Cancer Res. 2008 Feb 1;14(3):701-9
18245529
Mol Pathol. 2001 Apr;54(2):57-79
11322167
Crit Rev Oncog. 1994;5(6):589-613
8519812
J Cell Biol. 2006 Nov 20;175(4):563-9
17101694
Mol Pathol. 2001 Aug;54(4):275-80
11477145
Oncogene. 2005 Jun 23;24(27):4349-61
15824736
Biochem Biophys Res Commun. 2008 Apr 11;368(3):808-14
18275847
Mol Cell Biol. 1992 Jan;12(1):10-21
1309586
J Biol Chem. 2003 Jun 27;278(26):24200-8
12695522
Mol Pathol. 1999 Apr;52(2):84-91
10474687
J Cell Biochem. 2006 Sep 1;99(1):105-16
16598765
Cancer Genet Cytogenet. 2001 Oct 15;130(2):105-10
11675130
J Cell Biochem. 2007 Aug 15;101(6):1475-91
17340618
Am J Pathol. 2002 Mar;160(3):849-59
11891184
Cell Commun Signal. 2006 Aug 08;4:6
16895594
Trends Biochem Sci. 2008 Oct;33(10):461-73
18789696