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Reply to: Hippo signalling maintains ER expression and ER+ breast cancer growth

Nature volume 591, pages E11–E12 (2021)Cite this article

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The Original Article was published on 03 March 2021

Replying to: S. Ma et al. Nature https://doi.org/10.1038/s41586-020-03131-5 (2021)

In the accompanying Comment, Ma et al.1 report that LATS1 and LATS2 (hereafter, LATS1/2) are required to maintain expression of oestrogen receptor-α (ERα), as deletion of LATS1/2 by CRISPR–Cas9 abolishes ESR1 mRNA and ERα protein in ERα+ breast cancer cell lines. We have previously reported the effects of LATS1/2 on human normal breast cell fate by depleting LATS1/2 using short hairpin RNAs (shRNAs) in primary human breast epithelial cells2. We showed that a reduction in the levels of LATS1/2 increases ESR1 mRNA and ERα protein, and favours the luminal phenotype in the normal breast. We next investigated whether the LATS kinases regulate ERα protein levels directly, by using luminal human breast cancer cells that express ERα endogenously. In contrast to Ma et al.1, we found that downregulation of LATS1/2 upregulates ERα protein and target genes, and that the expression of full-length LATS1 or LATS1 that lacks the kinase domain decreases levels of ERα. These discrepancies require clarification, and here we provide some possible explanations for the different outcomes of interfering with LATS1/2 expression and/or activity in ERα+ breast cancer cell lines.

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References

  1. Ma, S. et al. Hippo signalling maintains ER expression and ER+ breast cancer growth. Nature, https://doi.org/10.1038/s41586-020-03131-5 (2021).

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Authors and Affiliations

  1. Department of Biomedicine, University of Basel, University Hospital Basel, Basel, Switzerland

    Adrian Britschgi, Joana Pinto Couto & Mohamed Bentires-Alj

Authors
  1. Adrian Britschgi
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  2. Joana Pinto Couto
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  3. Mohamed Bentires-Alj
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Contributions

A.B., J.P.C. and M.B.-A. wrote the response. The author list for this Reply differs from the author list of the original Article to accelerate the response to the Comment.

Corresponding author

Correspondence to Mohamed Bentires-Alj.

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Competing interests

A.B. is an employee of Roche Pharma AG and J.P.C. of Novartis. M.B.-A. and A.B. are inventors on the US patent WO2016046768A1 ‘Lats and breast cancer’.

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Britschgi, A., Couto, J.P. & Bentires-Alj, M. Reply to: Hippo signalling maintains ER expression and ER+ breast cancer growth. Nature 591, E11–E12 (2021). https://doi.org/10.1038/s41586-020-03132-4

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