Nuclear localization of the transcriptional coactivator YAP is associated with invasive lobular breast cancer

Eva J. Vlug, Robert A.H. Van De Ven, Jeroen F. Vermeulen, Peter Bult, Paul J. Van Diest, Patrick W.B. Derksen

Research output: Contribution to journalArticlepeer-review

49 Scopus citations

Abstract

Background Yes Associated Protein (YAP) has been implicated in the control of organ size by regulating cell proliferation and survival. YAP is a transcriptional coactivator that controls cellular responses through interaction with TEAD transcription factors in the nucleus, while its transcriptional functions are inhibited by phosphorylation-dependent translocation to the cytosol. YAP overexpression has been associated with different types of cancer, such as lung, skin, prostate, ovary and liver cancer. Recently, YAP was linked to Ecadherin- dependent regulation of contact inhibition in breast cancer cells. Results In this study we examined YAP protein expression and cellular localization in 237 cases of human invasive breast cancer by immunohistochemistry and related its expression to clinicopathological features and E-cadherin expression. We observed that invasive lobular carcinoma is characterized by higher expression levels of both nuclear and cytosolic YAP (p<0.001). Nuclear YAP expression did not associate with other variables such as lymph node involvement, tumor grade, tumor size, mitotic activity or the molecular sub-types of invasive breast cancer. We observed that high nuclear and cytosolic YAP expression are associated with the E-cadherin deficient breast cancer subtype ILC (p<0.001) and cell lines derived from human breast cancers and conditional mouse models of human lobular breast cancer. Conclusions Since our data indicate that nuclear YAP localization is more common in breast cancers lacking functional adherens junctions, it suggests that YAP-mediated transcription may be involved in the development and progression of invasive lobular breast cancer.

Original languageEnglish (US)
Pages (from-to)375-384
Number of pages10
JournalCellular Oncology
Volume36
Issue number5
DOIs
StatePublished - Oct 2013
Externally publishedYes

Keywords

  • Adhesion
  • Breast cancer
  • Invasive Lobular Carcinoma
  • Yap (Hippo) signaling

ASJC Scopus subject areas

  • Molecular Medicine
  • Oncology
  • Cancer Research

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