Identification of IGFBP-6 as an effector of the tumor suppressor activity of SEMA3B.

Abstract

SEMA3B, a member of class 3 semaphorins, is a tumor suppressor. Competition with vascular endothelial growth factor (VEGF)165 explains a portion of the activity, whereas the VEGF-independent mechanism was not elucidated. We employed a microarray and screened for the genes whose expression was increased by SEMA3B in NCI-H1299 cells. Insulin-like growth factor-binding protein-6 (IGFBP-6), a tumor suppressor, showed greatest difference in the expression level. Introduction of IGFBP-6 cDNA reduced colony formation both on the dish surface and in soft agar. Insulin-like growth factor II, which antagonizes IGFBP-6, partly abrogated the effect. Inhibition of IGFBP-6 by small interfering RNA diminished the sub-G0/G1 population that was induced by SEMA3B and abrogated the growth suppressive effect of SEMA3B. We concluded that IGFBP-6 is the effector of tumor suppressor activity of SEMA3B in NCI-H1299 cells. It has been reported that beta-catenin suppresses the expression of IGFBP-6. Introduction of beta-catenin into the cells partly abrogated the growth suppressive effect of SEMA3B. Our result indicates that semaphorin signaling and beta-catenin signaling converge on IGFBP-6 and antithetically affect their functions.

• Authors: N Koyama, J Zhang, Huqun, H Miyazawa, T Tanaka, X Su, K Hagiwara
• Journal: Oncogene (Oncogene) Vol. 27 Issue 51 Pg. 6581-9 (Nov 20 2008) ISSN: 1476-5594 [Electronic] England
• PMID: 18985860 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• CTNNB1 protein, human
• Insulin-Like Growth Factor Binding Protein 6
• Membrane Glycoproteins
• RNA, Small Interfering
• SEMA3B protein, human
• Semaphorins
• TCF Transcription Factors
• Tumor Suppressor Proteins
• beta Catenin

Topics

• Cell Proliferation (drug effects)
• Cells, Cultured
• Humans
• Insulin-Like Growth Factor Binding Protein 6 (antagonists & inhibitors, genetics, physiology)
• Membrane Glycoproteins (genetics, metabolism, physiology)
• Protein Binding
• RNA, Small Interfering (pharmacology)
• Semaphorins (genetics, metabolism, physiology)
• Signal Transduction (drug effects)
• TCF Transcription Factors (metabolism)
• Transfection
• Tumor Stem Cell Assay
• Tumor Suppressor Proteins (metabolism, physiology)
• beta Catenin (metabolism)