Oncoprotein SET dynamically regulates cellular stress response through nucleocytoplasmic transport in breast cancer.
Cell Biol Toxicol
; 39(4): 1795-1814, 2023 08.
Article
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| MEDLINE
| ID: mdl-36534342
ABSTRACT
SETß is the predominant isoform of oncoprotein SE translocation (SET) in various breast cancer cell lines. Interactome-transcriptome analysis has shown that SETß is intimately associated with cellular stress response. Among various exogenous stimuli, formaldehyde (FA) causes distinct biological effects in a dose-dependent manner. In response to FA at different concentrations, SET dynamically shuttles between the nucleus and cytoplasm, performing diverse biofunctions to restore homeostasis. At a low concentration, FA acts as an epidermal growth factor (EGF) and activates the HER2 receptor and downstream signaling pathways in HER2+ breast cancer cells, resulting in enhanced cell proliferation. Nucleocytoplasmic transport of SETß is controlled by the PI3K/PKCα/CK2α axis and depletion or blockade of the transport of SETß suppresses EGF-induced activation of AKT and ERK. SETß also inhibits not only stress-induced activation of p38 MAPK signaling pathway, but also assembly of stress granules by hindering formation of the G3BP1-RNA complex. Our findings suggest that SET functions as an important regulator which modulates cellular stress signaling pathways dynamically.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Neoplasias de la Mama
/
Factor de Crecimiento Epidérmico
Límite:
Female
/
Humans
Idioma:
En
Revista:
Cell Biol Toxicol
Asunto de la revista:
TOXICOLOGIA
Año:
2023
Tipo del documento:
Article