SATB2 suppresses the progression of colorectal cancer cells via inactivation of MEK5/ERK5 signaling

Mohammed A. Mansour, Toshinori Hyodo, Satoko Ito, Kenji Kurita, Toshio Kokuryo, Keisuke Uehara, Masato Nagino, Masahide Takahashi, Michinari Hamaguchi, Takeshi Senga

Research output: Contribution to journalArticle

37 Citations (Scopus)

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. SATB2 is a transcription factor with multiple roles in embryonic development. SATB2 expression was reduced in colorectal cancer tissues and its expression suppressed migration, invasion and proliferation of colorectal cancer cells. Tumor-suppressive function of SATB2 was mediated by inactivation of MEK5/ERK5 signaling pathway. Our finding presents a novel SATB2 function on colorectal cancer.

Original languageEnglish
Pages (from-to)1394-1405
Number of pages12
JournalFEBS Journal
Volume282
Issue number8
DOIs
Publication statusPublished - 01-04-2015

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'SATB2 suppresses the progression of colorectal cancer cells via inactivation of MEK5/ERK5 signaling'. Together they form a unique fingerprint.

  • Cite this

    Mansour, M. A., Hyodo, T., Ito, S., Kurita, K., Kokuryo, T., Uehara, K., Nagino, M., Takahashi, M., Hamaguchi, M., & Senga, T. (2015). SATB2 suppresses the progression of colorectal cancer cells via inactivation of MEK5/ERK5 signaling. FEBS Journal, 282(8), 1394-1405. https://doi.org/10.1111/febs.13227