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The deadly cross-talk between Hippo pathway and epithelial–mesenchymal transition (EMT) in cancer

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Abstract

Hippo signaling pathway is an evolutionarily conserved network that regulates organ size growth and tissue regeneration. Hippo signaling dysfunction results in uncontrolled cell proliferation and influences cell differentiation. Aberrant Hippo pathway signaling is implicated in cancer progression, by promoting cell proliferation, cancer stem cell properties, chemoresistance and metastatic capacity. Epithelial–mesenchymal transition (EMT) is also well known to be implicated in carcinogenesis. Loss of cell polarity, disruption of cell–cell junctions and cytoskeletal remodeling are essential during EMT. At the same time, signals related to intercellular contact, cell-extracellular matrix contact, polarity and mechanotransduction are included in the list of regulatory inputs into Hippo pathway. Therefore, the emerging association between Hippo pathway and EMT in cancer is not surprising. Recent studies have begun to unravel the mechanisms of interaction between Hippo signaling pathway and EMT. In this review, we describe the existing evidence of cross talk between Hippo signaling pathway key molecules and the process of EMT, with emphasis on the role of Hippo—EMT interplay in cancer.

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Abbreviations

CAPG:

Gelsolin-like actin-capping protein

CRC:

Colorectal cancer

CSC:

Scancer stem cells

EMT:

Epithelial–mesenchymal transition

HCC:

Hepatocellular carcinoma

HIF1A:

Hypoxia-inducible factor-1α

LATS1/2:

Large tumor suppressor 1/2 kinases

MOB1A/B:

MOB kinase activator 1A/B

MSTs:

Mammalian sterile 20-like kinases

NA:

NEDD8-activating enzyme

OSCC:

Oral squamous cell carcinoma

SAV1:

Salvador homolog 1

TAZ:

Transcriptional co-activator with PDZ-binding motif

TEAD:

TEA domain family

WWC:

WW-and-C2-domain-containing proteins

YAP:

Yes-associated protein

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  1. Department of General Surgery, University General Hospital of Patras, 26504, Rion, Greece

    Ioanna Akrida

  2. Department of Anatomy-Histology-Embryology, University of Patras Medical School, Rion, Greece

    Ioanna Akrida, Vasiliki Bravou & Helen Papadaki

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Akrida, I., Bravou, V. & Papadaki, H. The deadly cross-talk between Hippo pathway and epithelial–mesenchymal transition (EMT) in cancer. Mol Biol Rep 49, 10065–10076 (2022). https://doi.org/10.1007/s11033-022-07590-z

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