Burnett, Riesa M.Craven, Kelly E.Krishnamurthy, PurnaGoswami, Chirayu P.Badve, SunilCrooks, PeterMathews, William P.Bhat-Nakshatri, PoornimaNakshatri, Harikrishna2016-07-132016-07-132015-05-20Burnett, R. M., Craven, K. E., Krishnamurthy, P., Goswami, C. P., Badve, S., Crooks, P., … Nakshatri, H. (2015). Organ-specific adaptive signaling pathway activation in metastatic breast cancer cells. Oncotarget, 6(14), 12682–12696.1949-2553https://hdl.handle.net/1805/10369Breast cancer metastasizes to bone, visceral organs, and/or brain depending on the subtype, which may involve activation of a host organ-specific signaling network in metastatic cells. To test this possibility, we determined gene expression patterns in MDA-MB-231 cells and its mammary fat pad tumor (TMD-231), lung-metastasis (LMD-231), bone-metastasis (BMD-231), adrenal-metastasis (ADMD-231) and brain-metastasis (231-BR) variants. When gene expression between metastases was compared, 231-BR cells showed the highest gene expression difference followed by ADMD-231, LMD-231, and BMD-231 cells. Neuronal transmembrane proteins SLITRK2, TMEM47, and LYPD1 were specifically overexpressed in 231-BR cells. Pathway-analyses revealed activation of signaling networks that would enable cancer cells to adapt to organs of metastasis such as drug detoxification/oxidative stress response/semaphorin neuronal pathway in 231-BR, Notch/orphan nuclear receptor signals involved in steroidogenesis in ADMD-231, acute phase response in LMD-231, and cytokine/hematopoietic stem cell signaling in BMD-231 cells. Only NF-κB signaling pathway activation was common to all except BMD-231 cells. We confirmed NF-κB activation in 231-BR and in a brain metastatic variant of 4T1 cells (4T1-BR). Dimethylaminoparthenolide inhibited NF-κB activity, LYPD1 expression, and proliferation of 231-BR and 4T1-BR cells. Thus, transcriptome change enabling adaptation to host organs is likely one of the mechanisms associated with organ-specific metastasis and could potentially be targeted therapeutically.en-USAttribution 3.0 United StatesBreast NeoplasmsgeneticspathologyGene Expression Regulation, NeoplasticphysiologyNeoplasm MetastasisSignal TransductionTranscriptomeArticle