Elevation of YAP promotes the epithelial-mesenchymal transition and tumor aggressiveness in colorectal cancer

Ling, Hsiang-Hsi; Kuo, Chih Chia; Lin, Bo; Huang, Yen-Hua; Lin, Cheng

doi:10.1016/j.yexcr.2016.11.024

Cited by 84 publications

(77 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Importantly, Hippo effectors YAP and TAZ were also found to regulate EMT (Lei et al, ; Diepenbruck et al, ; Ling et al, ) and are mechanoregulators of TGF‐β–Smad signaling (Szeto et al, ). The cytoskeleton translates environmental stimuli to gene expression through the regulation of mechanosensitive signaling pathways, such as the Rho‐MRTF and the Hippo target proteins TAZ and YAP.…”

Section: Regulation Of Mrtf Function During Emtmentioning

confidence: 99%

MRTFs‐ master regulators of EMT

Gasparics

Sebe

2017

Developmental Dynamics

View full text Add to dashboard Cite

Recent evidence implicates the myocardin-related transcription factors (MRTFs) as key mediators of the phenotypic plasticity leading to the conversion of various cell types into myofibroblasts. This review highlights the function of MRTFs during development, fibrosis and cancer, and the role of MRTFs during epithelial-mesenchymal transitions (EMTs) underlying these processes. EMT is a sequentially orchestrated process where cells undergo a rearrangement of their cell contacts and activate a fibrogenic and myogenic expression program. MRTFs interact with and regulate the major signaling pathways and the expression of key markers and transcription factors involved in EMT. These functions indicate a central role for MRTFs in controlling the process of EMT. Developmental Dynamics 247:396-404,

show abstract

Section: Regulation Of Mrtf Function During Emtmentioning

confidence: 99%

MRTFs‐ master regulators of EMT

Gasparics

Sebe

2017

Developmental Dynamics

View full text Add to dashboard Cite

show abstract

“…[ 64 ] The capacity of HCT116 cells to migrate invasively in a transwell assay in vitro was also strongly impaired by transfection with siRNAs against YAP and TAZ. [ 65,66 ] Although there is some indirect evidence for a role of YAP in CRC metastasis, [ 67 ] and knocking down YAP reduced LoVo cell lung met‐induced lesions by around half after injection into the tail vein of NOD/SCID mice, [ 68 ] further work is needed to investigate YAP/TAZ function in improved models for CRC metastasis. Overall, the existing evidence strongly indicates a role for YAP in CRC tumor growth and suggests a possible role in invasion and metastasis.…”

Section: Introductionmentioning

confidence: 99%

YAP/TAZ: Drivers of Tumor Growth, Metastasis, and Resistance to Therapy

2020

View full text Add to dashboard Cite

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

show abstract

“…For example, YAP gene amplification was found in liver cancer and TNBC 10,11 . Besides, experimental studies revealed that YAP controlled several cancers' biological behaviors, such as carcinogenesis, cell survival and "stemness" maintenance 12,13 . In TNBC, population based studies showed that Hippo signaling activation related to TNBC breast cancer risk 14 .…”

Section: Introductionmentioning

confidence: 99%

Regulation of Hippo signaling and triple negative breast cancer progression by an ubiquitin ligase RNF187

Wang

Kong

et al. 2020

Oncogenesis

View full text Add to dashboard Cite

Breast cancer is the most common malignancy for women worldwide, while Triple Negative Breast Cancer (TNBC) accounts for 20% in all patients. Compared with estrogen receptor positive breast cancer, which could be effectively controlled via endocrine therapy, TNBC is more aggressive and worse in prognosis. It is therefore urgent and necessary to develop a novel therapeutic strategy for TNBC treatment. Recent studies identified Hippo signaling is highly activated in TNBC, which could be a driving pathway for TNBC progression. In our study, we determine RNF187 as a negative regulator for Hippo signaling activation. RNF187 depletion significantly decreases cell migration and invasion capacity in TNBC. These effects could be rescued by further YAP depletion. Depletion of RNF187 increases the YAP protein level and Hippo signaling target genes, such as CTGF and CYR61 in TNBC. Immuno-precipitation assay shows that RNF187 associates with YAP, promoting its degradation possibly via inducing YAP K48-dependent polyubiquitination. Interestingly, Our clinical data reveals that RNF187 reversely correlates with YAP protein level and Hippo target genes. RNF187 tends to correlate with good prognosis in TNBC patients. Our study provides evidence to establish a proteolytic mechanism in regulation Hippo signaling activation in TNBC.

show abstract

Elevation of YAP promotes the epithelial-mesenchymal transition and tumor aggressiveness in colorectal cancer

Cited by 84 publications

References 40 publications

MRTFs‐ master regulators of EMT

MRTFs‐ master regulators of EMT

YAP/TAZ: Drivers of Tumor Growth, Metastasis, and Resistance to Therapy

Regulation of Hippo signaling and triple negative breast cancer progression by an ubiquitin ligase RNF187

Contact Info

Product

Resources

About