title: Bone morphogenetic protein 2 (BMP2) induces growth suppression and enhances chemosensitivity of human colon cancer cells.
abstract: BACKGROUND
  Molecular profiling of colorectal cancer (CRC) based on global gene expression has revealed multiple dysregulated signalling pathways associated with drug resistance and poor prognosis. However, the role of BMP2 signaling in CRC is not fully characterised.
  
  
  METHODS
  Bioinformatics data analysis were conducted on the GSE21510 dataset. Leniviral technology was utilized to stably express BMP2 in the HCT116 CRC model. Gene expression profiling was conducted using Agilent microarray platform while data normalization and bioinformatics were conducted using GeneSpring software. Changes in gene expression were assessed using qRT-PCR. AlamarBlue assay was used to assess cell viability in vitro. In vivo experiments were conducted using SCID mice.
  
  
  RESULTS
  Our data revealed frequent downregulation of BMP2 in primary CRC tissues. Additionally, interrogation of publically available gene expression datasets revealed significant downregulation of BMP2 in metastatic recurrent compared to non-metastatic cancer (p = 0.02). Global gene expression analysis in CRC cells over-expressing BMP2 revealed multiple dysregulated pathways mostly affecting cell cycle and DNA damage response. Concordantly, lentiviral-mediated re-expression of BMP2 inhibited HCT116 CRC growth, sphere formation, clonogenic potential, cell migration, and sensitized CRC cells to 5-fluorouracil (5-FU) in vitro. Additionally, BMP2 inhibited CRC tumor formation in SCID mice.
  
  
  CONCLUSIONS
  Our data revealed an inhibitory role for BMP2 in CRC, suggesting that restoration of BMP2 expression could be a potential therapeutic strategy for CRC.
authors.affiliation: Stem Cell Unit, Department of Anatomy, College of Medicine, King Saud University, Riyadh, 11461 Kingdom of Saudi Arabia.
authors.forename: Radhakrishnan
authors.initials: R
authors.lastname: Vishnubalaji
authors.affiliation: Princess Margaret Cancer Centre, University Health Network, Toronto, ON Canada.
authors.forename: Shijun
authors.initials: S
authors.lastname: Yue
authors.affiliation: Stem Cell Unit, Department of Anatomy, College of Medicine, King Saud University, Riyadh, 11461 Kingdom of Saudi Arabia.
authors.forename: Musaad
authors.initials: M
authors.lastname: Alfayez
authors.affiliation: Molecular Endocrinology Unit (KMEB), Department of Endocrinology, University Hospital of Odense and University of Southern Denmark, Odense, Denmark.
authors.forename: Moustapha
authors.initials: M
authors.lastname: Kassem
authors.affiliation: Princess Margaret Cancer Centre, University Health Network, Toronto, ON Canada.
authors.forename: Fei-Fei
authors.initials: FF
authors.lastname: Liu
authors.affiliation: Stem Cell Unit, Department of Anatomy, College of Medicine, King Saud University, Riyadh, 11461 Kingdom of Saudi Arabia ; Prince Naif Health Research Center, King Saud University, Riyadh, 11461 Kingdom of Saudi Arabia.
authors.forename: Abdullah
authors.initials: A
authors.lastname: Aldahmash
authors.affiliation: Stem Cell Unit, Department of Anatomy, College of Medicine, King Saud University, Riyadh, 11461 Kingdom of Saudi Arabia.
authors.forename: Nehad M
authors.initials: NM
authors.lastname: Alajez
keywords: Bone morphogenetic protein2 (BMP2); Chemosensitivity; Colon cancer