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

S. D. Chou, A. Murshid, Takanori Eguchi, J. Gong, S. K. Calderwood

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)2178-2188
Number of pages11
JournalOncogene
Volume34
Issue number17
DOIs
Publication statusPublished - Jun 16 2014
Externally publishedYes

Fingerprint

Catenins
Shock
Hot Temperature
Breast Neoplasms
Long Noncoding RNA
Sirolimus
Carcinogenesis
Breast
Phosphorylation
Messenger RNA
Stem Cell Factor
RNA-Binding Proteins
Serine
Transcription Factors
Phosphotransferases
Epithelial Cells
Neoplasm Metastasis

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics
  • Medicine(all)

Cite this

HSF1 regulation of β-catenin in mammary cancer cells through control of HuR/elavL1 expression. / Chou, S. D.; Murshid, A.; Eguchi, Takanori; Gong, J.; Calderwood, S. K.

In: Oncogene, Vol. 34, No. 17, 16.06.2014, p. 2178-2188.

Research output: Contribution to journalArticle

Chou, S. D. ; Murshid, A. ; Eguchi, Takanori ; Gong, J. ; Calderwood, S. K. / HSF1 regulation of β-catenin in mammary cancer cells through control of HuR/elavL1 expression. In: Oncogene. 2014 ; Vol. 34, No. 17. pp. 2178-2188.
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