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E-GEOD-48432 - Amplification of RANK- and c-Met-mediated signaling promotes metastatic colonization

Status
Released on 6 February 2014, last updated on 3 June 2014
Organism
Homo sapiens
Samples (4)
Array (1)
Protocols (7)
Description
We found that RANKL, expressed by cancer cells or derived from exogenous sources, consistently induced human prostate, breast, kidney, lung and liver cancer cells to colonize or metastasize to bone in an animal model of cancer bone metastasis. RANK-mediated signaling established a premetastatic niche through a forward feedback loop by inducing RANKL and c-Met expression and downstream signaling via upregulation of master regulator transcription factors regulating EMT (Twist1, Slug, Zeb1, Zeb2), stem cells (Sox2, Myc, Oct3/4 and Nanog), neuroendocrine cells (Sox 9, HIF-1α and FoxA2) and osteomimicry (c-Myc/Max, Sox2, Sox9, HIF1α and Runx2). Abrogating RANK or its downstream signaling network, c-Myc/Max or c-Met, abolished PCa skeletal metastasis in mice. We observed that a small number of RANKL-expressing PCa cells can initiate bone and soft tissue metastases by recruiting non-tumorigenic or bystander PCa or host cells from the circulation or at metastatic sites to co-colonize bone. The recruited bystander PCa cells assume the phenotypes of RANKL-expressing PCa cells by expressing increased c-Met, phosphorylated c-Met and RANKL. RANKL expression at a single cell level in primary PCa tissues predicted disease-specific survival, reflecting the significant role of RANKL-RANK signaling in the development of lethal bone metastasis. Global gene expression analysis perturbed by RANKL in LNRANKL compared to LNNeo cells.
Experiment type
transcription profiling by array 
Contacts
Sungyong You <refrigence@gmail.com>, Gina C Chu, Leland W Chung, Michael R Freeman
Citation
RANK- and c-Met-mediated signal network promotes prostate cancer metastatic colonization. Chu GC, Zhau HE, Wang R, Rogatko A, Feng X, Zayzafoon M, Liu Y, Farach-Carson MC, You S, Kim J, Freeman MR, Chung L. , PMID:24478054
MIAME
PlatformsProtocolsVariablesProcessedRaw
Files
Investigation descriptionE-GEOD-48432.idf.txt
Sample and data relationshipE-GEOD-48432.sdrf.txt
Raw data (1)E-GEOD-48432.raw.1.zip
Processed data (1)E-GEOD-48432.processed.1.zip
Array designA-AFFY-44.adf.txt
Links