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2017 ; 8
(4
): e2733
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C/EBP? LIP augments cell death by inducing osteoglycin
#MMPMID28383550
Wassermann-Dozorets R
; Rubinstein M
Cell Death Dis
2017[Apr]; 8
(4
): e2733
PMID28383550
show ga
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/EBP? regulates the expression of Ogn. C/EBP? 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.
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