Unknown

Dataset Information

0

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


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 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.

SUBMITTER: Burnett RM 

PROVIDER: S-EPMC4494966 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature

altmetric image

Publications

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

Burnett Riesa M RM   Craven Kelly E KE   Krishnamurthy Purna P   Goswami Chirayu P CP   Badve Sunil S   Crooks Peter P   Mathews William P WP   Bhat-Nakshatri Poornima P   Nakshatri Harikrishna H  

Oncotarget 20150501 14


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 brain-metastasis (231-BR) variants. When gene expression between metastases was compared, 231-BR cell  ...[more]

Similar Datasets

| S-ECPF-GEOD-66495 | biostudies-other
| S-EPMC2596479 | biostudies-literature
| S-EPMC5386761 | biostudies-literature
| S-EPMC5564317 | biostudies-literature
| S-EPMC5899649 | biostudies-literature
| S-EPMC8263651 | biostudies-literature
| S-EPMC4832137 | biostudies-literature
| S-EPMC8059100 | biostudies-literature
| S-EPMC8002348 | biostudies-literature
| S-EPMC7763959 | biostudies-literature