English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Metastatic tumor cells engage the local tumor microenvironment and activate specific pro-survival mechanisms to thrive and progress in the harsh bone marrow niche. Here we show that the major contributors to the survival of carcinoma cells that have colonized the bone marrow are the adipocyte-induced oxidative stress and ER stress pathways. We demonstrate that upon exposure to adipocyte-rich environments  in vitro  or  in vivo , bone-trophic prostate and breast tumor cells upregulate the oxidative stress enzyme, HO-1. We also show that HO-1 levels are significantly increased in human metastatic prostate cancer tissues and that stable HO-1 overexpression in tumor cells promotes growth and invasiveness. Co-incident with the adipocyte-induced expression of HO-1, there is an upregulation of ER chaperone BIP and splicing of XBP1, indicating adipocyte-driven unfolded protein response, a process that we show to be sensitive to antioxidant treatment. Importantly, we also demonstrate that triggering of the oxidative stress and ER stress responses, or HO-1 induction by adipocyte exposure result in the activation of pro-survival pathways, involving survivin. Collectively, our findings reveal a new link between HO-1 and survivin expression in tumor cells, and provide a new insight into potentially targetable survival pathways in bone-metastatic disease.

Adipocyte-activated oxidative and ER stress pathways promote tumor survival in bone via upregulation of Heme Oxygenase 1 and Survivin