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.

journal_name

Oncogene

journal_title

Oncogene

authors

Koyama N,Zhang J,Huqun,Miyazawa H,Tanaka T,Su X,Hagiwara K

doi

10.1038/onc.2008.263

subject

Has Abstract

pub_date

2008-11-20 00:00:00

pages

6581-9

issue

51

eissn

0950-9232

issn

1476-5594

journal_volume

27

pub_type

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