Phosphorylation of 14-3-3ζ links YAP transcriptional activation to hypoxic glycolysis for tumorigenesis DOI Creative Commons
Yu Jia, Huiyan Li, Jue Wang

и другие.

Oncogenesis, Год журнала: 2019, Номер 8(5)

Опубликована: Май 10, 2019

Abstract Hypoxic microenvironment deregulates metabolic homeostasis in cancer cells albeit the underlying mechanisms involved this process remain hitherto enigmatic. 14-3-3ζ/Yes-associated protein (YAP) axis plays a principal role malignant transformation and tumor development. Here, we report that hypoxia disassembles 14-3-3ζ from YAP thereby promotes nuclear localization mediated by ERK2, which directly binds to D-site of mitogen-activated kinase (MAPK) docking domain Leu98/100 phosphorylates at Ser37. When localizing nucleus, recruits pyruvate M2 (PKM2) gene promoter with hypoxia-inducible factor 1α (HIF-1α), for PKM2 transcription is required. Ser37 phosphorylation instrumental hypoxia-induced glucose uptake, lactate production, clonogenicity pancreatic ductal adenocarcinoma (PDAC) cells, as well tumorigenesis mice. The positively correlates p-ERK1/2 activity HIF-1α expression clinical samples patients PDAC predicts unfavorable prognosis. Our findings underscore an appreciable linkage between transcriptional activation hypoxic glycolysis governed ERK2-dependent progression PDAC.

Язык: Английский

Genetic and biological hallmarks of colorectal cancer DOI Open Access
Jiexi Li, Xingdi Ma, Deepavali Chakravarti

и другие.

Genes & Development, Год журнала: 2021, Номер 35(11-12), С. 787 - 820

Опубликована: Июнь 1, 2021

Colorectal cancer has served as a genetic and biological paradigm for the evolution of solid tumors, these insights have illuminated early detection, risk stratification, prevention, treatment principles. Employing hallmarks framework, we provide conceptual framework to understand how alterations in colorectal drive cell biology properties shape heterotypic interactions across cells tumor microenvironment. This review details research advances pertaining genetics cancer, emerging concepts gleaned from immune single-cell profiling, critical remaining knowledge gaps influencing development effective therapies this that remains major public health burden.

Язык: Английский

Процитировано

382
Photodynamic therapy for hypoxic tumors: Advances and perspectives DOI
Huang Li,

Shaojing Zhao,

Jiasheng Wu

и другие.

Coordination Chemistry Reviews, Год журнала: 2021, Номер 438, С. 213888 - 213888

Опубликована: Март 16, 2021

Язык: Английский

Процитировано

260
YAP/TAZ: Drivers of Tumor Growth, Metastasis, and Resistance to Therapy DOI Creative Commons
Barry J. Thompson

BioEssays, Год журнала: 2020, Номер 42(5)

Опубликована: Март 4, 2020

Abstract The transcriptional co‐activators YAP (or YAP1) and TAZ WWTR1) are frequently activated during the growth progression of many solid tumors, including lung, colorectal, breast, pancreatic, liver carcinomas as well melanoma glioma. YAP/TAZ bind to TEAD‐family drive cancer cell survival, proliferation, invasive migration, metastasis. activation may also confer resistance chemotherapy, radiotherapy, or immunotherapy. YAP‐TEAD cooperates with RAS‐induced AP‐1 (FOS/JUN) transcription factor tumor MRTF‐SRF promote cancer‐associated fibroblasts, matrix stiffening, key upstream repressor is Hippo (MST1/2‐LATS1/2) pathway activators mechanically induced Integrin‐SRC E‐cadherin‐AJUBA/TRIP6/LIMD1, PI3K‐AKT, inflammation‐induced G‐protein coupled receptor (GPCR) signals, all which antagonize pathway. In this review, strategies target activity in discussed along prospects for synergy established pillars therapy.

Язык: Английский

Процитировано

226
Methylation of GPRC5A promotes liver metastasis and docetaxel resistance through activating mTOR signaling pathway in triple negative breast cancer DOI Creative Commons

Xueqi Ou,

Yeru Tan, Jindong Xie

и другие.

Drug Resistance Updates, Год журнала: 2024, Номер 73, С. 101063 - 101063

Опубликована: Фев. 1, 2024

This study aims to explore the function and mechanism of G Protein-coupled receptor class C group 5 member A (GPRC5A) in docetaxel-resistance liver metastasis breast cancer.

Язык: Английский

Процитировано

90
The force loading rate drives cell mechanosensing through both reinforcement and cytoskeletal softening DOI Creative Commons
Ion Andreu, Bryan Falcones,

Sebastian Hurst

и другие.

Nature Communications, Год журнала: 2021, Номер 12(1)

Опубликована: Июль 9, 2021

Abstract Cell response to force regulates essential processes in health and disease. However, the fundamental mechanical variables that cells sense respond remain unclear. Here we show rate of application (loading rate) drives mechanosensing, as predicted by a molecular clutch model. By applying dynamic regimes through substrate stretching, optical tweezers, atomic microscopy, find increasing loading rates trigger talin-dependent leading adhesion growth reinforcement, YAP nuclear localization. above given threshold actin cytoskeleton softens, decreasing preventing reinforcement. stretching rat lungs vivo, similar phenomenon may occur. Our results cell sensing external forces passive parameters (like tissue stiffness) can be understood same mechanisms, driven properties under mechanosensing molecules involved.

Язык: Английский

Процитировано

90
GPCR-Hippo Signaling in Cancer DOI Creative Commons
Jiaqian Luo, Fa‐Xing Yu

Cells, Год журнала: 2019, Номер 8(5), С. 426 - 426

Опубликована: Май 8, 2019

The Hippo signaling pathway is involved in tissue size regulation and tumorigenesis. Genetic deletion or aberrant expression of some genes lead to enhanced cell proliferation, tumorigenesis, cancer metastasis. Recently, multiple studies have identified a wide range upstream regulators the pathway, including mechanical cues ligands G protein-coupled receptors (GPCRs). Through activation related proteins possibly rearrangements actin cytoskeleton, GPCR can potently modulate phosphorylation states activity YAP TAZ, two homologous oncogenic transcriptional co-activators, major effectors pathway. Herein, we summarize network, regulation, functions GPCR-Hippo signaling, will also discuss potential anti-cancer therapies targeting GPCR-YAP signaling.

Язык: Английский

Процитировано

85
MiR-103a-3p promotes tumour glycolysis in colorectal cancer via hippo/YAP1/HIF1A axis DOI Creative Commons
Zhenqiang Sun, Qiuge Zhang, Weitang Yuan

и другие.

Journal of Experimental & Clinical Cancer Research, Год журнала: 2020, Номер 39(1)

Опубликована: Ноя. 20, 2020

Abstract Background Glycolysis plays an essential role in the growth and metastasis of solid cancer has received increasing attention recent years. However, complex regulatory mechanisms tumour glycolysis remain elusive. This study aimed to explore molecular effect mechanism noncoding RNA miR-103a-3p on colorectal (CRC). Methods We explored effects biological functions CRC cells vitro vivo. Furthermore, we investigated whether regulates HIF1A expression through Hippo/YAP1 pathway, evaluated miR-103a-3p-LATS2/SAV1-YAP1-HIF1A axis promoting angiogenesis contributed invasion cells. Results found that was highly expressed tissues cell lines compared with matched controls high associated poor patient prognosis. Under hypoxic conditions, a level promoted proliferation, invasion, migration, Moreover, knockdown inhibited growth, Hippo-YAP1 signalling pathway nude mice xenograft model. Here, demonstrated could directly target LATS2 SAV1. Subsequently, verified TEAD1, transcriptional coactivator Yes-associated protein 1 (YAP1), bound promoter region YAP1 TEAD1 proteins co-regulated HIF1A, thus glycolysis. Conclusions MiR-103a-3p, which is cells, promotes by targeting core molecules SAV1 contributing enhanced CRC. Our revealed functional miR-103a-3p/YAP1/HIF1A glycolysis, would provide potential intervention targets for targeted therapy

Язык: Английский

Процитировано

74
Mechanical control of nuclear import by Importin-7 is regulated by its dominant cargo YAP DOI Creative Commons
María García-García,

Sara Sánchez-Perales,

Patricia Jarabo

и другие.

Nature Communications, Год журнала: 2022, Номер 13(1)

Опубликована: Март 4, 2022

Abstract Mechanical forces regulate multiple essential pathways in the cell. The nuclear translocation of mechanoresponsive transcriptional regulators is an step for mechanotransduction. However, how mechanical import process not understood. Here, we identify a highly transport receptor (NTR), Importin-7 (Imp7), that drives YAP, key regulator mechanotransduction pathways. Unexpectedly, YAP governs mechanoresponse Imp7 by forming YAP/Imp7 complex responds to cues through Hippo kinases MST1/2. Furthermore, behaves as dominant cargo Imp7, restricting binding and other cargoes such Smad3 Erk2. Thus, additional regulatory layer indirectly regulated cues, which activate preferential cargo, competes out cargoes, resulting signaling crosstalk.

Язык: Английский

Процитировано

67
Endothelial YAP/TAZ Signaling in Angiogenesis and Tumor Vasculature DOI Creative Commons
Aukie Hooglugt, Miesje M. van der Stoel, Reinier A. Boon

и другие.

Frontiers in Oncology, Год журнала: 2021, Номер 10

Опубликована: Фев. 4, 2021

Solid tumors are dependent on vascularization for their growth. The hypoxic, stiff, and pro-angiogenic tumor microenvironment induces angiogenesis, giving rise to an immature, proliferative, permeable vasculature. vessels promote metastasis complicate delivery of anti-cancer therapies. In many types tumors, YAP/TAZ activation is correlated with increased levels angiogenesis. addition, endothelial important the formation new blood lymphatic during development. Oncogenic in cell growth invasion has been studied great detail, however role within endothelium remains insufficiently understood, which complicates therapeutic strategies aimed at targeting cancer. Here, we overview upstream signals from that control explore downstream targets driving We further discuss potential treatments vascular normalization improve

Язык: Английский

Процитировано

61
Defining cellular complexity in human autosomal dominant polycystic kidney disease by multimodal single cell analysis DOI Creative Commons
Yoshiharu Muto, Eryn E. Dixon, Yasuhiro Yoshimura

и другие.

Nature Communications, Год журнала: 2022, Номер 13(1)

Опубликована: Окт. 30, 2022

Abstract Autosomal dominant polycystic kidney disease (ADPKD) is the leading genetic cause of end stage renal characterized by progressive expansion cysts. To better understand cell types and states driving ADPKD progression, we analyze eight five healthy human samples, generating single multiomic atlas consisting ~100,000 nucleus transcriptomes ~50,000 epigenomes. Activation proinflammatory, profibrotic signaling pathways are driven proximal tubular cells with a failed repair transcriptomic signature, proinflammatory fibroblasts collecting duct cells. We identify GPRC5A as marker for cyst-lining that exhibits increased transcription factor binding motif availability NF-κB, TEAD, CREB retinoic acid receptors. validate distal enhancer regulating expression containing these motifs. This analysis reveals previously unrecognized cellular heterogeneity provides foundation to develop diagnostic therapeutic approaches.

Язык: Английский

Процитировано

61