The Hippo pathway is an evolutionally conserved signaling cascade that controls organ size and tissue regeneration under physiological conditions, and its aberrations have been well studied to promote tumor initiation and progression. Dysregulation of the Hippo tumor suppressor signaling frequently occurs in gastric cancer (GC) and other solid tumors and contributes to cancer development through modulating multiple aspects, including cell proliferation, survival, metastasis, and oncotherapy resistance. In the clinic, Hippo components also possess diagnostic and prognostic values for cancer patients. Considering its crucial role in driving tumorigenesis, targeting the Hippo pathway may greatly benefit developing novel cancer therapies. This review summarizes the current research progress regarding the core components and regulation of the Hippo pathway, as well as the mechanism and functional roles of their dysregulation in gastrointestinal malignancies, especially in GC, and discusses the therapeutic potential of targeting the Hippo pathway against cancers.
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http://dx.doi.org/10.3390/biomedicines10102512 | DOI Listing |
J Med Chem
January 2025
Key Laboratory of Protection, Development and Utilization of Medicinal Resources in Liupanshan Area, Ministry of Education, School of Pharmacy, Ningxia Medical University, 1160 Shengli Street, Yinchuan, Ningxia Province 750004, China.
Genetic mutations in components of the Hippo pathway frequently lead to the aberrant activation of TEADs, which is often associated with cancer. Consequently, TEADs have been actively pursued as therapeutic targets for diseases driven by TEAD overactivation. In this study, we report two series of TEAD PROTACs based on CRBN binders and VHL binders.
View Article and Find Full Text PDFBiochim Biophys Acta Mol Basis Dis
January 2025
Department of Radiation Oncology, Zhujiang Hospital, Southern Medical University, Guangzhou City, Guangdong Province 510280, China. Electronic address:
Background: Oxaliplatin is the first-line chemotherapy for patients with colon cancer (CC). However, its resistance limits its therapeutic efficacy.
Methods: Oxaliplatin resistance-associated differentially expressed genes (DEGs) in the GSE42387 and GSE227315 datasets were identified through bioinformatics methods.
Cancers (Basel)
December 2024
Department of Neurosurgery, Baylor College of Medicine, Houston, TX 77030, USA.
: With the rise in prevalence of diagnostic genetic techniques like RNA sequencing and whole exome sequencing (WES), as well as biological treatment regiments for cancer therapy, several genes have been implicated in carcinogenesis. This review aims to update our understanding of the Neurofibromatosis 2 (NF2) gene and its role in the pathogenesis of various cancers. : A comprehensive search of five online databases yielded 43 studies that highlighted the effect of sporadic NF2 mutations on several cancers, including sporadic meningioma, ependymoma, schwannoma, mesothelioma, breast cancer, hepatocellular carcinoma, prostate cancer, glioblastoma, thyroid cancer, and melanoma.
View Article and Find Full Text PDFJ Transl Med
January 2025
Department of Oncology, The Second Hospital of Nanjing, Affiliated to Nanjing University of Chinese Medicine, Nanjing, 210003, China.
Background: Almonertinib is the initial third-generation EGFR-TKI in China, but its resistance mechanism is unknown. Cancer-associated fibroblasts (CAFs) are essential matrix components in the tumor microenvironment, but their impact on almonertinib resistance is unknown. This study aimed to explore the correlation between CAFs and almonertinib resistance in non-small cell lung cancer (NSCLC).
View Article and Find Full Text PDFNat Commun
January 2025
The Department of Urology, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University, Shanghai, 200233, China.
Balanced self-renewal and differentiation of stem cells are crucial for maintaining tissue homeostasis, but the underlying mechanisms of this process remain poorly understood. Here, from an RNA interference (RNAi) screen in adult Drosophila intestinal stem cells (ISCs), we identify a factor, Pax, which is orthologous to mammalian PXN, coordinates the proliferation and differentiation of ISCs during both normal homeostasis and injury-induced midgut regeneration in Drosophila. Loss of Pax promotes ISC proliferation while suppressing its differentiation into absorptive enterocytes (ECs).
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