HSF1 regulation of β-catenin in mammary cancer cells through control of HuR/elavL1 expression

There is now compelling evidence to indicate a place for heat shock factor 1 (HSF1) in mammary carcinogenesis, tumour progression and metastasis. Here we have investigated a role for HSF1 in regulating the expression of the stem cell renewal factor β-catenin in immortalized human mammary epithelial...

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Bibliographic Details
Published in:Oncogene 2015-04, Vol.34 (17), p.2178-2188
Main Authors: Chou, Shiuh-Dih, Murshid, Ayesha, Eguchi, Takanori, Gong, Jianlin, Calderwood, Stuart K
Format: Article
Language:English
Subjects:
beta Catenin - biosynthesis
beta Catenin - genetics
Breast cancer
Breast Neoplasms - genetics
Breast Neoplasms - metabolism
Breast Neoplasms - pathology
Carcinogenesis
Cell Line, Tumor
Development and progression
DNA-Binding Proteins - genetics
DNA-Binding Proteins - metabolism
ELAV Proteins - genetics
ELAV Proteins - metabolism
ELAV-Like Protein 1
Female
Gene expression
Gene Expression Regulation, Neoplastic
Genetic aspects
Health aspects
Heat shock factors
Heat shock proteins
Heat Shock Transcription Factors
HSF1 protein
Humans
HuR protein
Kinases
Metastases
Neoplasm Proteins - genetics
Neoplasm Proteins - metabolism
Non-coding RNA
Phosphorylation
Rapamycin
RNA, Long Noncoding - genetics
RNA, Long Noncoding - metabolism
RNA-binding protein
Serine
Stem cells
TOR protein
TOR Serine-Threonine Kinases - genetics
TOR Serine-Threonine Kinases - metabolism
Transcription Factors - genetics
Transcription Factors - metabolism
Translation
Tumors
β-Catenin
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Summary:There is now compelling evidence to indicate a place for heat shock factor 1 (HSF1) in mammary carcinogenesis, tumour progression and metastasis. Here we have investigated a role for HSF1 in regulating the expression of the stem cell renewal factor β-catenin in immortalized human mammary epithelial and carcinoma cells. We found HSF1 to be involved in regulating the translation of β-catenin, by investigating effects of gain and loss of HSF1 on this protein. Interestingly, although HSF1 is a potent transcription factor, it was not directly involved in regulating levels of β-catenin mRNA. Instead, our data suggest a complex role in translational regulation. HSF1 was shown to regulate levels of the RNA-binding protein HuR that controlled β-catenin translation. An extra complexity was added to this scenario when it was shown that the long non-coding RNA molecule lincRNA-p21, known to be involved in β-catenin mRNA (CTNNB1) translational regulation, was controlled by HSF1 repression. We have shown previously that HSF1 was positively regulated through phosphorylation by mammalian target of rapamycin (mTOR) kinase on a key residue, serine 326, essential for transcriptional activity. In this study, we found that mTOR knockdown not only decreased HSF1-S326 phosphorylation in mammary cells, but also decreased β-catenin expression through a mechanism requiring HuR. Our data point to a complex role for HSF1 in the regulation of HuR and β-catenin expression that may be significant in mammary carcinogenesis.
ISSN:0950-9232
1476-5594
DOI:10.1038/onc.2014.177