TEAD4: A key regulator of tumor metastasis and chemoresistance - Mechanisms and therapeutic implications

• Published in: Biochimica et biophysica acta. Reviews on cancer 2024-01, Vol.1879 (1), p.189050-189050, Article 189050
• Main Authors: Liu, Mohan, Hu, Weina, Meng, Xiaona, Wang, Biao
• Format: Article
• Language: English
• Subjects: cancer metastasis; Chemoresistance; Drug Resistance, Neoplasm; Epithelial-mesenchymal transition; Epithelial-Mesenchymal Transition - physiology; Humans; Neoplasms - drug therapy; Neoplasms - genetics; Neoplasms - pathology; TEA Domain Transcription Factors; TEAD4; Transcription Factors - genetics; Transcription Factors - metabolism; Tumor Microenvironment
• ISSN: 0304-419X; 1879-2561
• DOI: 10.1016/j.bbcan.2023.189050

Cancer metastasis is a complex process influenced by various factors, including epithelial-mesenchymal transition (EMT), tumor cell proliferation, tumor microenvironment, and cellular metabolic status, which remains a significant challenge in clinical oncology, accounting for a majority of cancer-related deaths. TEAD4, a key mediator of the Hippo signaling pathway, has been implicated in regulating these factors that are all critical in the metastatic cascade. TEAD4 drives tumor metastasis and chemoresistance, and its upregulation is associated with poor prognosis in many types of cancers, making it an attractive target for therapeutic intervention. TEAD4 promotes EMT by interacting with coactivators and activating the transcription of genes involved in mesenchymal cell characteristics and extracellular matrix remodeling. Additionally, TEAD4 enhances the stemness of cancer stem cells (CSCs) by regulating the expression of genes associated with CSC maintenance. TEAD4 contributes to metastasis by modulating the secretion of paracrine factors and promoting heterotypic cellular communication. In this paper, we highlight the central role of TEAD4 in cancer metastasis and chemoresistance and its impact on various aspects of tumor biology. Understanding the mechanistic basis of TEAD4-mediated processes can facilitate the development of targeted therapies and combination approaches to combat cancer metastasis and improve treatment outcomes. •TEAD4 drives metastasis via regulating EMT, TME and metabolism.•TEAD4 induces chemoresistance by upregulating drug efflux and anti-apoptotic proteins.•Targeting TEAD4 represents a promising cancer therapy.