open access

Vol 53, No 2 (2015)
Review paper
Submitted: 2015-07-03
Accepted: 2015-07-08
Published online: 2015-07-09
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The Hippo pathway in colorectal cancer

Piotr M. Wierzbicki, Agnieszka Rybarczyk
DOI: 10.5603/FHC.a2015.0015
·
Pubmed: 26160682
·
Folia Histochem Cytobiol 2015;53(2):105-119.

open access

Vol 53, No 2 (2015)
REVIEW
Submitted: 2015-07-03
Accepted: 2015-07-08
Published online: 2015-07-09

Abstract

Colorectal cancer (CRC) is one the most frequently diagnosed neoplastic diseases worldwide. Currently, aside from traditional chemotherapy, advanced CRCs are treated with modern drugs targeting cellular components such as epithelial growth factor receptor (EGFR). Since up to 70% of metastasized CRCs are drug resistant, the description of recent progress in cellular homeostasis regulation may shed new light on the development of new molecular targets in cancer treatment. The Hippo pathway has recently become subject of intense investigations since it plays a crucial role in cell proliferation, differentiation, apoptosis and tumourigenesis. Components of the Hippo pathway are deregulated in various human malignancies, and expression levels of its major signal transducers were proposed as prognostic factors in colorectal cancer. In this review we focused on recent data regarding Hippo pathway, its up-stream signals and down-stream effectors. Hippo negatively regulates its major effectors, YAP1 and TAZ kinases, which act as transcriptional co-activators inducing expression of genes involved not only in tissue repair and proliferation but are also oncoproteins involved in tumour development and progression. The deregulation of Hippo pathway components was found in many malignancies. The interactions between Hippo and Wnt/β-catenin signalling, crucial in the maintenance of cell homeostasis, have been described in relation to the control of intestinal stem cell proliferation and CRC development. The recently discovered positive feedback loop between activated YAP1 and increased EGFR/KRAS signalling found in oesophageal, ovarian and hepatocellular cancer has been related to the CRC progression and resistance to EGFR inhibitors during CRC therapy.

Abstract

Colorectal cancer (CRC) is one the most frequently diagnosed neoplastic diseases worldwide. Currently, aside from traditional chemotherapy, advanced CRCs are treated with modern drugs targeting cellular components such as epithelial growth factor receptor (EGFR). Since up to 70% of metastasized CRCs are drug resistant, the description of recent progress in cellular homeostasis regulation may shed new light on the development of new molecular targets in cancer treatment. The Hippo pathway has recently become subject of intense investigations since it plays a crucial role in cell proliferation, differentiation, apoptosis and tumourigenesis. Components of the Hippo pathway are deregulated in various human malignancies, and expression levels of its major signal transducers were proposed as prognostic factors in colorectal cancer. In this review we focused on recent data regarding Hippo pathway, its up-stream signals and down-stream effectors. Hippo negatively regulates its major effectors, YAP1 and TAZ kinases, which act as transcriptional co-activators inducing expression of genes involved not only in tissue repair and proliferation but are also oncoproteins involved in tumour development and progression. The deregulation of Hippo pathway components was found in many malignancies. The interactions between Hippo and Wnt/β-catenin signalling, crucial in the maintenance of cell homeostasis, have been described in relation to the control of intestinal stem cell proliferation and CRC development. The recently discovered positive feedback loop between activated YAP1 and increased EGFR/KRAS signalling found in oesophageal, ovarian and hepatocellular cancer has been related to the CRC progression and resistance to EGFR inhibitors during CRC therapy.

Get Citation

Keywords

CRC; Hippo pathway; YAP1/TAZ; Wnt signalling; EGFR/KRAS; intestinal stem cells

About this article
Title

The Hippo pathway in colorectal cancer

Journal

Folia Histochemica et Cytobiologica

Issue

Vol 53, No 2 (2015)

Article type

Review paper

Pages

105-119

Published online

2015-07-09

DOI

10.5603/FHC.a2015.0015

Pubmed

26160682

Bibliographic record

Folia Histochem Cytobiol 2015;53(2):105-119.

Keywords

CRC
Hippo pathway
YAP1/TAZ
Wnt signalling
EGFR/KRAS
intestinal stem cells

Authors

Piotr M. Wierzbicki
Agnieszka Rybarczyk

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