Gene expression profiling and pathway analysis identify the integrin signaling pathway to be altered by IL-1β in human pancreatic cancer cells: role of JNK.
The pro-inflammatory cytokine, IL-1β, is a critical component of the persistent inflammatory milieu that pancreatic cancer cells frequently encounter. Although several studies report diverse mechanisms responsible for this association, yet a comprehensive global analysis of the effect of IL-1β in these cells is not clearly evident. In this study, we performed whole genome transcriptome analysis of control and IL-1β treated human pancreatic MIA PaCa-2 cells, validated the most targeted pathway and evaluated the role of JNK therein. 225 Genes were up-regulated and 1215 were down-regulated and these were categorized into biological processes and cellular pathways using the PANTHER classification system. The altered genes categorized into significant biological processes that included those of cell cycle, mitosis, transport and intracellular protein trafficking. The integrin signaling pathway emerged as harboring the maximum number of differentially expressed genes. Two important genes of this pathway, namely vinculin and α5-integrin were validated and both depicted significant inhibition by IL-1β that was prevented in the presence of JNK siRNA. In a wound healing assay, IL-1β increased the migratory rate of MIA PaCa-2 and Panc-1 cells that was abrogated by JNK inhibition. Additionally, vinculin and α-integrin siRNAs also increased the migration of these cells along the wound edge. These results suggest that in these pancreatic cancer cells, IL-1β inhibits components of the integrin signaling pathway in a JNK dependent manner that contributes to their increased migratory potential. Therefore, JNK might be potentially targeted to prevent the migration and invasion of pancreatic cancer cells.
CSIR-Institute of Genomics and Integrative Biology, Mall Road, Delhi 110 007, India.
Gaurav
G
Verma
Himanshi
H
Bhatia
Malabika
M
Datta
D045744:Cell Line, Tumor; D015536:Down-Regulation; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D039482:Integrin alpha5 / Q000378:metabolism*; D053583:Interleukin-1beta / Q000494:pharmacology*; D048670:MAP Kinase Kinase 4 / Q000235:genetics / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation; D016596:Vinculin / Q000037:antagonists & inhibitors / Q000378:metabolism
D039482:Integrin alpha5; D053583:Interleukin-1beta; D034741:RNA, Small Interfering; C488955:VCL protein, human; D016596:Vinculin; D048670:MAP Kinase Kinase 4