title: SATB2 suppresses the progression of colorectal cancer cells via inactivation of MEK5/ERK5 signaling.
abstract: Special AT-rich sequence binding protein 2 (SATB2) is an evolutionarily conserved transcription factor that has multiple roles in neuronal development, osteoblast differentiation, and craniofacial patterning. SATB2 binds to the nuclear matrix attachment region, and regulates the expression of diverse sets of genes by altering chromatin structure. Recent studies have reported that high expression of SATB2 is associated with favorable prognosis in colorectal and laryngeal cancer; however, it remains uncertain whether SATB2 has tumor-suppressive functions in cancer cells. In this study, we examined the effects of SATB2 expression on the malignant characteristics of colorectal cancer cells. Expression of SATB2 repressed the proliferation of cancer cells in vitro and in vivo, and also suppressed their migration and invasion. Extracellular signal-regulated kinase 5 (ERK5) is a mitogen-activated protein kinase that is associated with an aggressive phenotype in various types of cancer. SATB2 expression reduced the activity of ERK5, and constitutive activation of ERK5 restored the proliferation, anchorage-independent growth, migration and invasion of SATB2-expressing cells. Our results demonstrate the existence of a novel regulatory mechanism of SATB2-mediated tumor suppression via ERK5 inactivation.
authors: Division of Cancer Biology, Nagoya University Graduate School of Medicine, Nagoya, Japan; Biochemistry Section, Department of Chemistry, Faculty of Science, Tanta University, Egypt.
authors: Mohammed A
authors: MA
authors: Mansour
authors: Toshinori
authors: T
authors: Hyodo
authors: Satoko
authors: S
authors: Ito
authors: Kenji
authors: K
authors: Kurita
authors: Toshio
authors: T
authors: Kokuryo
authors: Keisuke
authors: K
authors: Uehara
authors: Masato
authors: M
authors: Nagino
authors: Masahide
authors: M
authors: Takahashi
authors: Michinari
authors: M
authors: Hamaguchi
authors: Takeshi
authors: T
authors: Senga
mesh_terms: D000328:Adult; D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D002448:Cell Adhesion; D002465:Cell Movement; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D048671:MAP Kinase Kinase 5 / Q000235:genetics / Q000378:metabolism*; D008297:Male; D036961:Matrix Attachment Region Binding Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D048054:Mitogen-Activated Protein Kinase 7 / Q000235:genetics / Q000378:metabolism*; D009367:Neoplasm Staging; D010766:Phosphorylation; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D014945:Wound Healing; D023041:Xenograft Model Antitumor Assays
chemical_list: D036961:Matrix Attachment Region Binding Proteins; D012333:RNA, Messenger; C521297:SATB2 protein, human; D014157:Transcription Factors; D048054:Mitogen-Activated Protein Kinase 7; D048671:MAP Kinase Kinase 5; C482563:MAP2K5 protein, human
keywords: ERK5; SATB2; colorectal cancer; invasion; migration