Gene mutations are involved in the development of malignant mesothelioma. Important mutations have been identified in the genes for cyclin-dependent kinase inhibitor 2A (p16) alternative reading frame, breast cancer-associated protein 1 () and neurofibromatosis type 2 (). Previously, the utility of detecting the loss of by immunohistochemistry (IHC) and p16-deletion by fluorescence hybridization has been identified in several studies. However, -associated examinations have not been performed. The present study aimed to evaluate the expression of yes-associated protein 1 (YAP1) and tafazzin (TAZ) protein, which are associated with gene mutations, in malignant mesothelioma (MM) and reactive mesothelial cells (RMCs). Formalin-fixed paraffin-embedded tissues from 31 MM and 33 RMC samples were analyzed. The expression of YAP1 and TAZ protein were examined by IHC. Positivity for YAP1 was identified 27/31 MM and 15/33 RMC samples. Positivity for TAZ was identified in 28/31 MM and 18/33 RMC samples. Using the optimal cutoff points determined by the receiver operating characteristic curve, a positive IHC result for YAP1 and TAZ was 74% sensitive and 94% specific for detecting MM. The results indicate that increased expression of YAP1 and TAZ may be associated with mesothelial tumorization, and aid in the diagnosis of MM.
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http://dx.doi.org/10.3892/ol.2018.8225 | DOI Listing |
Elife
January 2025
Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Cigarette smoking is a well-known risk factor inducing the development and progression of various diseases. Nicotine (NIC) is the major constituent of cigarette smoke. However, knowledge of the mechanism underlying the NIC-regulated stem cell functions is limited.
View Article and Find Full Text PDFiScience
December 2024
Department of Molecular Physiology & Biophysics, Vanderbilt University, Nashville, TN, USA.
Increased blood amino acid levels (hyperaminoacidemia) stimulate pancreas expansion by unclear mechanisms. Here, by genetic and pharmacological disruption of glucagon receptor (GCGR) in mice and zebrafish, we found that the ensuing hyperaminoacidemia promotes pancreatic acinar cell proliferation and cell hypertrophy, which can be mitigated by a low protein diet in mice. In addition to mammalian target of rapamycin complex 1 (mTORC1) signaling, acinar cell proliferation required , the most highly expressed amino acid transporter gene in both species.
View Article and Find Full Text PDFMol Biol Rep
December 2024
State Key Laboratory of Cell Differentiation and Regulation, College of Life Sciences, Henan Normal University, Xinxiang, 453007, China.
Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) are key downstream effectors of the Hippo pathway that regulate organ size, tissue homeostasis, and cancer development. YAP/TAZ play crucial regulatory roles in organ growth, cell proliferation, cell renewal, and regeneration. Mechanistically, YAP/TAZ influence the occurrence and progression of liver regeneration (LR) through various signaling pathways, including Notch, Wnt/β-catenin, TGF-β/Smad.
View Article and Find Full Text PDFJ Cell Mol Med
December 2024
Laboratoire d'Oncologie Moléculaire, Département de Chimie, Université du Québec à Montréal, Montreal, Quebec, Canada.
The Hippo pathway plays a tumorigenic role in highly angiogenic glioblastoma (GBM), whereas little is known about clinically relevant Hippo pathway inhibitors' ability to target adaptive mechanisms involved in GBM chemoresistance. Their molecular impact was investigated here in vitro against an alternative process to tumour angiogenesis termed vasculogenic mimicry (VM) in GBM-derived cell models. In silico analysis of the downstream Hippo signalling members YAP1, TAZ and TEAD1 transcript levels in low-grade glioblastoma (LGG) and GBM tumour tissues was performed using GEPIA.
View Article and Find Full Text PDFKRAS mutations are frequent in various human cancers. The development of selective inhibitors targeting KRAS mutations has opened a new era for targeted therapy. However, intrinsic and acquired resistance to these inhibitors remains a major challenge.
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