Organ-specific adaptive signaling pathway activation in metastatic breast cancer cells

Riesa M. Burnett, Kelly E. Craven, Purna Krishnamurthy, Chirayu P. Goswami, Sunil Badve, Peter Crooks, William P. Mathews, Poornima Bhat-Nakshatri, Harikrishna Nakshatri

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Breast 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 brainmetastasis (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 organspecific metastasis and could potentially be targeted therapeutically.

Original languageEnglish
Pages (from-to)12682-12696
Number of pages15
JournalOncotarget
Volume6
Issue number14
StatePublished - 2015

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Breast Neoplasms
Neoplasm Metastasis
Gene Expression
Semaphorins
Orphan Nuclear Receptors
Activation Analysis
Bone and Bones
Acute-Phase Reaction
Brain
Hematopoietic Stem Cells
Transcriptome
Adipose Tissue
Neoplasms
Oxidative Stress
Breast
Cytokines
Lung
Pharmaceutical Preparations
Proteins

Keywords

  • Brain metastasis
  • Breast cancer
  • DMAPT
  • NF-kB
  • TMEM47

ASJC Scopus subject areas

  • Oncology

Cite this

Burnett, 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.

Organ-specific adaptive signaling pathway activation in metastatic breast cancer cells. / Burnett, Riesa M.; Craven, Kelly E.; Krishnamurthy, Purna; Goswami, Chirayu P.; Badve, Sunil; Crooks, Peter; Mathews, William P.; Bhat-Nakshatri, Poornima; Nakshatri, Harikrishna.

In: Oncotarget, Vol. 6, No. 14, 2015, p. 12682-12696.

Research output: Contribution to journalArticle

Burnett, RM, Craven, KE, Krishnamurthy, P, Goswami, CP, Badve, S, Crooks, P, Mathews, WP, Bhat-Nakshatri, P & Nakshatri, H 2015, 'Organ-specific adaptive signaling pathway activation in metastatic breast cancer cells', Oncotarget, vol. 6, no. 14, pp. 12682-12696.
Burnett RM, Craven KE, Krishnamurthy P, Goswami CP, Badve S, Crooks P et al. Organ-specific adaptive signaling pathway activation in metastatic breast cancer cells. Oncotarget. 2015;6(14):12682-12696.
Burnett, Riesa M. ; Craven, Kelly E. ; Krishnamurthy, Purna ; Goswami, Chirayu P. ; Badve, Sunil ; Crooks, Peter ; Mathews, William P. ; Bhat-Nakshatri, Poornima ; Nakshatri, Harikrishna. / Organ-specific adaptive signaling pathway activation in metastatic breast cancer cells. In: Oncotarget. 2015 ; Vol. 6, No. 14. pp. 12682-12696.
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