Molecular Mechanisms of FAT Atypical Cadherin 1 (FAT1), the Hippo Pathway, and the Yes-Associated Protein (YAP) Signaling Pathways in Some Cancers

Sep 22, 2026

Review outlines how FAT atypical cadherin 1 (FAT1) and its integration with the Hippo signaling cascade regulate cell proliferation, differentiation, and apoptosis. The document highlights pathway dysregulation as a driver of tumorigenesis across cancers including head and neck squamous cell carcinoma, hepatocellular carcinoma, and breast cancer. It summarizes FAT1 as an ortholog of Drosophila fat, noting its frequent mutation and potential as a biomarker and therapeutic target, while focusing on FAT1, Hippo, and YAP gene mutations and expression impacts.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages12

Reading Time30 min

AccessFree to download

Abstract

Introduction

Physiological role of FAT1 as an adhesion molecule

Function of FAT1

Conclusion

REVIEW | Editorial Proc | ess: Submission:03/28/2025 Acceptance:02/26/2026 Published:03/06/2026 | | --- | --- | Molecular Mechanisms of FAT Atypical Cadherin 1 (FAT1), the Hippo Pathway, and the Yes-Associated Protein (YAP) Signaling Pathways in Some Cancers Roland Osei Saahene1, Precious Barnes2 *, Du-Bois Asante3, Sylvester Ackah Famieh4, Elvis Agbo5 Abstract Introuduction: FAT atypical cadherin 1 (FAT1), the Hippo pathway and Yes-associated protein (YAP) signaling play significant roles in cell proliferation, differentiation, and apoptosis. Dysregulation of these pathways contributes to tumorigenesis in multiple cancers, including head and neck squamous cell carcinoma (HNSCC), hepatocellular carcinoma (HCC), and breast cancer. Methods: The FATatypical cadherin 1 (FAT1) gene is an ortholog of the Drosophila fat gene, which encodes the protocadherin FAT1 . FAT1 is one of the most mutated genes and is therefore considered to be an emerging cancer biomarker and a potential therapeutic target for novel therapies. However, the molecular mechanisms of the FAT1 signaling pathways it mediates has not been fully elucidated. Results: The Hippo-YAP pathway is considered a crucial oncogenic pathway in multiple tumors. The expression of genes controlled by the Hippo downstream transcriptional coactivators Yes-associated protein 1 (YAP) is widely deregulated in different human cancers, including head and neck squamous cell carcinoma (HNSCC) . Conclusion: This review discusses the FAT1, Hippo and Yap genes, with a focus on their mutations and expression levels, and their impact on signaling pathways and mechanisms in various types of cancer. Keywords: STAT3-Wnt/β-catenin-EGFR family-HER Asian Pac J Cancer Prev, 27 (3), 793-804 Introduction FAT atypical cadherin 1 (FAT1) is a member of the FAT family of cadherins and is known for its large extracellular domain and cytoplasmic tail, which interact with intracellular signaling pathways. Its key functions include cell adhesion, regulation of the actin cytoskeleton, and tumor suppression through the modulation of Hippo signaling and inhibition of Hippo/Yes-associated protein (YAP) pathway activation. FAT1 plays different roles in different tissues or cancer types, it is considered an oncogene in cancers such as acute leukemia, hepatocellular carcinoma (HCC), glioblastoma (GMB), and gastric cancer; but is a tumor suppressor gene in HNSCC, ESCC, breast cancer, and cervical cancer [1] . The effect ofFAT1 mutation on malignant phenotypes has not been investigated, and there is a paucity of knowledge about its clinical implications. Physiological role of FAT1 as an adhesion molecule The FAT1 gene was first cloned from the human T-cell acute lymphoblastic leukemia (T-ALL) cell line and is located on chromosome 4q34-35 which consists of 27 exons [2] . FAT1 is a member of the cadherin-like protein family and is a transmembrane protein that encodes 4588 amino acid residues. It consists of 34 cadherin repeats, a laminin G domain, and five epidermal growth factor (EGF)-like repeats in the extracellular region, followed by a transmembrane region. Its C-terminal cytoplasmic tail contains a PDZ-binding motif [2](Figure 1) . Under normal physiological conditions, FAT1 is considered asa molecular “brake” during mitochondrial respiration [3], therefore, it controls the proliferation and migration of vascular smooth muscle cells during injury [4]. Moreover, it functions as a receptor during signaling pathways that regulate cell–cell interactions and planar cell polarity [5] The FAT1 gene is considered a transcriptional activator that binds elements that code with NFκB and E2F1 in its 1Department of Microbiology and Immunology, School of Medical Sciences, College of Health and Allied Sciences, University of Cape Coast, Ghana. 2Department of Chemical Pathology, School of Medical Sciences, College of Health and Allied Sciences, University of Cape Coast, Ghana. 3Department of Forensic Scien

FAQs

What roles do FAT1, the Hippo pathway, and YAP signaling play in cells?

They regulate cell proliferation, differentiation, and apoptosis. Dysregulation contributes to tumor development in multiple cancers.

Why is FAT1 considered a promising cancer biomarker or therapeutic target?

FAT1 is among the most frequently mutated genes. It is discussed as an emerging biomarker and potential target for novel therapies.

How does the review connect FAT1 to Hippo-YAP oncogenic signaling?

The Hippo-YAP pathway is described as a crucial oncogenic pathway. Gene expression controlled by YAP is reported as widely deregulated across human cancers, with FAT1 influencing Hippo signaling activity.

Sep 22, 2026

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