The transcriptional co-activator YAP: A new player in head and neck cancer

Publication date: November 2018

Source: Oral Oncology, Volume 86

Author(s): Carmen Segrelles, Jesús M. Paramio, Corina Lorz

Abstract

The Hippo-YAP (Yes-associated protein) pathway is a key regulator of tissue growth, organ size and stem cell function. More recently, a fundamental role for this pathway has emerged in stem cell function and tumorigenesis. Activation of the transcriptional co-activator YAP promotes cell-contact independent proliferation, epithelial to mesenchymal transition (EMT), cancer stem cell features and drug resistance. In this review, we describe the main components of the pathway, the microenvironment and the cell-intrinsic cues governing its activation, the downstream players of the pathway and the biological implications of their activation in the context of cancer. We will focus on the existing knowledge of this pathway in head and neck squamous carcinoma (HNSCC), its clinical value in this type of cancer as a marker of poor prognosis and resistance to therapy, as well as the most encouraging therapeutic strategies targeting the pathway.

Graphical abstract

The activation of the Hippo pathway effector Yes-associated protein (YAP) is modulated by different upstream cues. Phosphorylated YAP accumulates in the cytosol where it is targeted for degradation. In its active form, YAP translocates to the nucleus and acts as a transcriptional co-activator, binding to different transcription factors such as the TEA-domain transcription factor family (TEADs) to activate the transcription of tumour promoting genes. In the context of head and neck cancer, YAP activation is associated to malignant transformation, poor overall survival and disease free survival, resistance to chemotherapy and radiotherapy, and potential resistance to immunotherapy.

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