Hippo-YAP/TAZ signaling in breast cancer - Reciprocal regulation of microRNAs and implications in precision medicine

Sep 24, 2026

Breast cancer is a molecularly heterogeneous, common female malignancy, and recent therapy strategies aim to match molecular diversity with more biologically based treatments. The Hippo signaling pathway controls cell fate by regulating tissue size, regeneration, healing, and stem-cell survival, and it influences proliferation and apoptosis in multiple organs. Hippo signaling is driven by MST1/2 and LATS1/2 kinases that phosphorylate YAP and TAZ to suppress downstream gene expression. The review focuses on Hippo signaling mechanisms, their relevance to breast cancer, and how microRNAs reciprocally regulate Hippo pathway components and related networks.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages12

Reading Time30 min

AccessFree to download

Introduction

Hippo signaling pathway in breast cancer

Therapy approaches and molecular heterogeneity

Review article scope

miRNA regulation of Hippo signaling

Implications for precision medicine

Genes & Diseases (2024) 11, 760e771 Available online [at](at www.sciencedirect.com)[ www.sciencedirect.com](at www.sciencedirect.com) ScienceDirect journal [homepage:](homepage: www. keaipublishing. com/en/journals/genes-diseases)[ www. keaipublishing. com/en/journals/genes-diseases](homepage: www. keaipublishing. com/en/journals/genes-diseases) REVIEW ARTICLE Hippo-YAP/TAZ signaling in breast cancer: Reciprocal regulation of microRNAs and implications in precision medicine Farzad Sadri a, Seyede fatemeh Hosseini b, Zohreh Rezaei c,* , Mohammad Fereidouni d,* a Student Research Committee, Birjand University of Medical Sciences, Birjand 9717853577, Iran b Tabas School of Nursing, Birjand University of Medical Sciences, Birjand 9717853577, Iran c Department of Biology, University of Sistan and Baluchestan, Zahedan 9816745785, Iran d Cellular and Molecular Research Center, Birjand University of Medical Sciences, Birjand 9717853577, Iran Received 4 July 2022; received in revised form 9 December 2022; accepted 29 January 2023 Available online 23 March 2023 KEYWORDS Breast cancer; Hippo signaling; Large tumor suppressor kinase 1; microRNAs; PDZ-binding motif; Yes-associated protein Abstract Breast cancer is a molecularly heterogeneous disease and the most common female malignancy. In recent years, therapy approaches have evolved to accommodate molecular diversity, with a focus on more biologically based therapies to minimize negative consequences. To regulate cell fate in human breast cells, the Hippo signaling pathway has been associated with the alpha subtype of estrogen receptors. This pathway regulates tissue size, regeneration, and healing, as well as the survival of tissue-speciﬁc stem cells, proliferation, and apoptosis in a variety of organs, allowing for cell differentiation. Hippo signaling is mediated by the kinases MST1, MST2, LATS1, and LATS2, as well as the adaptor proteins SAV1 and MOB. These kinases phosphorylate the downstream effectors of the Hippo pathway, yes-associated protein (YAP), and transcriptional coactivator with PDZ-binding motif (TAZ), suppressing the expression of their downstream target genes. The Hippo signaling pathway kinase cascade plays a signiﬁcant role in all cancers. Understanding the principles of this kinase cascade would prevent the occurrence of breast cancer. In recent years, small noncoding RNAs, or microRNAs, have been implicated in the development of several malignancies, including breast cancer. The interconnections between miRNAs and Hippo signaling pathway core proteins in the breast, on the other hand, remain poorly understood. In this review, we focused on highlighting the Hippo signaling system, its key parts, its importance in breast cancer, and its regulation by miRNAs and other related pathways. * Corresponding author. E-mail addresses: [z.rezaie222@gmail.com](z.rezaie222@gmail.com) (Z. Rezaei), [dr.m.fereidouni@gmail.com](dr.m.fereidouni@gmail.com) (M. Fereidouni). Peer review under responsibility of Chongqing Medical University. [https://doi.org/10.1016/j.gendis.2023.01.017](https://doi.org/10.1016/j.gendis.2023.01.017) 2352-3042/ª 2023 The Authors. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co., Ltd. This is an open access article under the CC BY license ([http://creativecommons.org/licenses/by/4.0/](http://creativecommons.org/licenses/by/4.0/) ). ª 2023 The Authors. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co. , Ltd. This is an open access article under the CC BY license ([http://creativecommons.org/](http://creativecommons.org/)[ ](http://creativecommons.org/)[licenses/by/4.0/](licenses/by/4.0/) ) . Introduction Breast cancer is the most frequent female cancer and is amolecularly heterogeneous disease. It is frequently treated with chemotherapy and hormone therapy.1 ,2 Breast cancer develops as a result of aberrant cell or tissue proliferation within the breast glands.3 The maj

FAQs

What is the central role of the Hippo-YAP/TAZ pathway in breast cells?

Hippo signaling governs tissue size, regeneration, healing, and stem-cell survival, while also regulating proliferation and apoptosis. It does so by controlling YAP and TAZ activity through phosphorylation.

How do microRNAs relate to Hippo signaling in breast cancer?

MicroRNAs have been implicated in the development of malignancies, including breast cancer, and the review emphasizes that the interconnections between miRNAs and Hippo pathway core proteins in breast tissue remain insufficiently understood.

Why is Hippo pathway knowledge important for breast cancer treatment?

The review argues that understanding the Hippo kinase cascade and its regulation may help prevent or better address breast cancer biology, supporting more targeted, precision-medicine-aligned approaches.

Sep 24, 2026

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