Stratification and delineation of gastric cancer signaling by in vitro transcription factor activity profiling and integrative genomics.
Integrative functional genomic approaches are helpful in delineating the complex dysregulations in cancers. In the present study, in vitro activity profiling of 45 signaling pathway driven transcription factors in eight gastric cancer cell lines and direct comparison with genome-wide profiles of gastric tumors were performed and the integration resulted in the identification of three categories of factors/pathways: i) highly activated signaling pathways that stem from mutations are the critical oncogenic drivers, ii) constitutively activated stress responsive pathways which are activated not due to genetic alterations, and iii) consistently down-regulated nuclear receptor responsive factors. This functional profiling helps in discriminating therapeutic targets and signaling interactions.
Cancer Genetics Laboratory, Department of Genetics, Centre for Excellence in Genomic Sciences, School of Biological Sciences, Madurai Kamaraj University, Madurai, India.
Jayaprakash
J
Periasamy
Cancer Genetics Laboratory, Department of Genetics, Centre for Excellence in Genomic Sciences, School of Biological Sciences, Madurai Kamaraj University, Madurai, India.
Muthulakshmi
M
Muthuswami
Cancer Genetics Laboratory, Department of Genetics, Centre for Excellence in Genomic Sciences, School of Biological Sciences, Madurai Kamaraj University, Madurai, India.
Divya Bhaskar
DB
Rao
Duke-NUS Graduate Medical School Singapore, 8 College Road, Singapore.
Patrick
P
Tan
Cancer Genetics Laboratory, Department of Genetics, Centre for Excellence in Genomic Sciences, School of Biological Sciences, Madurai Kamaraj University, Madurai, India. Electronic address: kumar@oncocellomics.org.
Kumaresan
K
Ganesan
D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000378:metabolism; D020869:Gene Expression Profiling; D023281:Genomics; D006801:Humans; D009154:Mutation; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism*; D051153:Wnt Proteins / Q000378:metabolism; D000097809:Transcription Factor MTF-1
D004268:DNA-Binding Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D051153:Wnt Proteins; D000097809:Transcription Factor MTF-1
Gastric cancer; In vitro profiling; Integrative functional genomics; Signaling pathway; Transcription factor