Identification of IGFBP-6 as an effector of the tumor suppressor activity  of SEMA3B.
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.
Koyama
N
N
Department of Respiratory Medicine, Saitama Medical University, Saitama, Japan. nkoyama@saitama-med.ac.jp
Zhang
J
J
Huqun
Miyazawa
H
H
Tanaka
T
T
Su
X
X
Hagiwara
K
K
D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D006801:Humans; D018976:Insulin-Like Growth Factor Binding Protein 6 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D011485:Protein Binding; D034741:RNA, Small Interfering / Q000494:pharmacology; D039961:Semaphorins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects; D051820:TCF Transcription Factors / Q000378:metabolism; D014162:Transfection; D014410:Tumor Stem Cell Assay; D025521:Tumor Suppressor Proteins / Q000378:metabolism / Q000502:physiology*; D051176:beta Catenin / Q000378:metabolism
C495270:CTNNB1 protein, human; D018976:Insulin-Like Growth Factor Binding Protein 6; D008562:Membrane Glycoproteins; D034741:RNA, Small Interfering; C409766:SEMA3B protein, human; D039961:Semaphorins; D051820:TCF Transcription Factors; D025521:Tumor Suppressor Proteins; D051176:beta Catenin