PKCθ-induced phosphorylations control the ability of Fra-1 to stimulate gene expression and cancer cell migration.
Cancer Lett
; 385: 97-107, 2017 01 28.
Article
in En
| MEDLINE
| ID: mdl-27816489
ABSTRACT
The AP-1 transcription factor Fra-1 is aberrantly expressed in a large number of cancers and plays crucial roles in cancer development and progression by stimulating the expression of genes involved in these processes. However, the control of Fra-1 transactivation ability is still unclear and here we hypothesized that PKCθ-induced phosphorylation could be necessary to obtain a fully active Fra-1 protein. Using MCF7 stable cells overexpressing equivalent levels of unphosphorylated Fra-1 or PKCθ-phosphorylated Fra-1, we showed that PKCθ-induced phosphorylation of Fra-1 was crucial for the stimulation of MMP1 and IL6 expression. Consistently, we found a significant positive correlation between PRKCQ (coding for PKCθ) and MMP1 mRNA expression levels in human breast cancer samples. PKCθ-induced phosphorylations, in part at T217 and T227 residues, strongly and specifically increased Fra-1 transcriptional activity through the stimulation of Fra-1 transactivation domain, without affecting JUN factors. More importantly, these phosphorylations were required for Fra-1-induced migration of breast cancer cells and phosphorylated Fra-1 expression was enriched at the invasion front of human breast tumors. Taken together, our findings indicate that PKCθ-induced phosphorylation could be important for the function of Fra-1 in cancer progression.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Protein Kinase C
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Breast Neoplasms
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Biomarkers, Tumor
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Gene Expression Regulation, Neoplastic
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Cell Movement
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Proto-Oncogene Proteins c-fos
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Isoenzymes
Limits:
Female
/
Humans
Language:
En
Journal:
Cancer Lett
Year:
2017
Document type:
Article