C/EBPβ LIP augments cell death by inducing osteoglycin.

Abstract:

:Many types of tumor cell are devoid of the extracellular matrix proteoglycan osteoglycin (Ogn), but its role in tumor biology is poorly studied. Here we show that RNAi of Ogn attenuates stress-triggered cell death, whereas its overexpression increases cell death. We found that the transcription factor C/EBPβ regulates the expression of Ogn. C/EBPβ is expressed as a full-length, active form (LAP) and as a truncated, dominant-negative form (LIP), and the LIP/LAP ratio is positively correlated with the extent of cell death under stress. For example, we reported that drug-resistant tumor cells lack LIP altogether, and its supplementation abolished their resistance to chemotherapy and to endoplasmic reticulum (ER) stress. Here we further show that elevated LIP/LAP ratio robustly increased Ogn expression and cell death under stress by modulating the mitogen-activated protein kinase/activator protein 1 pathway (MAPK/AP-1). Our findings suggest that LIP deficiency renders tumor cell resistant to ER stress by preventing the induction of Ogn.

journal_name

Cell Death Dis

journal_title

Cell death & disease

authors

Wassermann-Dozorets R,Rubinstein M

doi

10.1038/cddis.2017.155

subject

Has Abstract

pub_date

2017-04-06 00:00:00

pages

e2733

issue

4

issn

2041-4889

pii

cddis2017155

journal_volume

8

pub_type

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