SRC activates TAZ for intestinal tumorigenesis and regeneration

Byun, Mi Ran; Hwang, Jae Ho; Kim, A. Rum; Kim, Kyung Min; Park, Jung Il; Oh, Ho Taek; Hwang, Eun Sook; Hong, Jeong Ho

doi:10.1016/j.canlet.2017.09.003

Cited by 26 publications

(32 citation statements)

References 42 publications

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“…So, our findings support the notion that TAZ localization could play a significant role in the causation of liver cirrhosis. Speculatively, an increase in the levels of TAZ may represent a posttranscriptional mechanism, because there was no significant difference in the expression of WWTR1 mRNA between cirrhotic and control I subjects . Also, other probable reasons for this observation might be the differences in the in vivo half‐lives of TAZ or a possible error in both protein and mRNA experiments .…”

Section: Discussionmentioning

confidence: 98%

Liver stiffness correlates with serum osteopontin and TAZ expression in human liver cirrhosis

Khajehahmadi

Mohagheghi

Nikeghbalian

et al. 2019

Annals of the New York Academy of Sciences

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The pivotal role of the extracellular matrix (ECM) as both a cause and consequence of liver fibrosis is striking. However, mechanotransducer molecules and profibrogenic factors induced by liver stiffness are still unclear. The current study aimed to investigate liver stiffness and its correlation with the expression of the transcriptional coactivator with PDZ‐binding motif (TAZ) and serum osteopontin (OPN) in human cirrhosis. In this case−control study, liver tissue stiffness was determined using atomic force microscopy in cirrhotic livers (n = 38) of different etiologies and in controls (n = 10). Immunohistochemical and qRT‐PCR analyses were performed to analyze TAZ expression. Besides, western blotting and ELISA were performed to assess liver Indian hedgehog and serum OPN levels, respectively. Liver stiffness, TAZ expression, and hepatic gene expression and serum protein levels of OPN were significantly increased in patients with cirrhosis compared with the control groups (all P < 0.001), specifically in autoimmune‐ and alcohol‐related cirrhosis. In cirrhotic patients, liver stiffness was significantly associated with the expression of nuclear TAZ and OPN. The correlation between matrix stiffness as a mechanical property, TAZ as a potential mechanotransducer, and OPN as a matricellular factor suggests possible effects of mechanical features of the ECM on the expression of the aforementioned profibrogenic markers, which is predominant in autoimmune‐ and alcohol‐related cirrhosis.

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Section: Discussionmentioning

confidence: 98%

Liver stiffness correlates with serum osteopontin and TAZ expression in human liver cirrhosis

Khajehahmadi

Mohagheghi

Nikeghbalian

et al. 2019

Annals of the New York Academy of Sciences

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“…Several studies have demonstrated that Src can promote YAP/TAZ activity through multiple independent mechanisms ( Figure 2 ) [ 85 , 244 , 245 , 246 , 247 , 248 , 249 , 250 , 251 , 252 , 253 , 254 , 255 , 256 , 257 , 258 , 259 , 260 ]. Src and other Src family kinases (SFKs) can directly phosphorylate YAP [ 85 , 251 , 253 , 255 , 256 , 261 ] and TAZ [ 257 ] to promote their protein stability and activity. Tyrosine phosphorylation of YAP by Src or Yes was also found to promote YAP interaction with T-Box 5 (TBX5) and β-Catenin [ 85 , 256 ] or Runt-related Transcription Factor 2 (RUNX2) [ 261 ].…”

Section: Therapeutic Potential Of Targeting Yap/taz-tead In Cancermentioning

confidence: 99%

“…Tyrosine phosphorylation of YAP by Src or Yes was also found to promote YAP interaction with T-Box 5 (TBX5) and β-Catenin [ 85 , 256 ] or Runt-related Transcription Factor 2 (RUNX2) [ 261 ]. Src phosphorylates YAP on Y357 and TAZ at Y316 [ 257 ], and a recent report found that Src also phosphorylates YAP on Y341 and Y394 [ 251 ]. Src can also influence other pathways that regulate YAP and TAZ.…”

Section: Therapeutic Potential Of Targeting Yap/taz-tead In Cancermentioning

confidence: 99%

YAP/TAZ Activation as a Target for Treating Metastatic Cancer

Warren

Xiao

2018

Cancers

140

131

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Yes-Associated Protein (YAP) and Transcriptional Co-activator with PDZ-binding Motif (TAZ) have both emerged as important drivers of cancer progression and metastasis. YAP and TAZ are often upregulated or nuclear localized in aggressive human cancers. There is abundant experimental evidence demonstrating that YAP or TAZ activation promotes cancer formation, tumor progression, and metastasis. In this review we summarize the evidence linking YAP/TAZ activation to metastasis, and discuss the roles of YAP and TAZ during each step of the metastatic cascade. Collectively, this evidence strongly suggests that inappropriate YAP or TAZ activity plays a causal role in cancer, and that targeting aberrant YAP/TAZ activation is a promising strategy for the treatment of metastatic disease. To this end, we also discuss several potential strategies for inhibiting YAP/TAZ activation in cancer and the challenges each strategy poses.

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“…S3). Also, it has been shown that YAP is activated by the IL-6-Src signaling axis (46), and an IL-6 signaling effector kinase, Src, enhances TAZ expression and stability (47). Thus, we also investigated the effect of the Src kinase inhibitor dasatinib on hepatocyte proliferation.…”

Section: Discussionmentioning

confidence: 99%

TAZ stimulates liver regeneration through interleukin‐6–induced hepatocyte proliferation and inhibition of cell death after liver injury

Kim

Park

et al. 2019

The FASEB Journal

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In response to liver injury, the liver undergoes a regeneration process to retain its mass and function. However, the regeneration mechanism has not been fully clarified. This study investigated the role of transcriptional coactivator with PDZ‐binding motif (TAZ), a Hippo‐signaling effector, in liver regeneration. We observed that TAZ stimulates liver regeneration after liver injury. After partial hepatectomy (PHx) or carbon tetrachloride damage, TAZ was required for liver regeneration to increase hepatic cell proliferation and resist hepatic apoptosis, which were decreased in liver‐specific TAZ knockout (LKO) mice. TAZ stimulated macrophage infiltration, resulting in IL‐6 production, which induced liver regeneration. In LKO mice, IL‐6–induced activation of signal transducer and activator of transcription 3, ERK, and PKB was decreased. We also observed that periductal fibrogenesis was significantly increased in LKO mice during liver regeneration after PHx, which was caused by increased hepatic apoptosis. Our results suggest that TAZ stimulates liver regeneration through IL‐6–induced hepatocyte proliferation and inhibition of cell death after liver injury.—Kim, A. R., Park, J. I., Oh, H. T., Kim, K. M., Hwang, J.‐H., Jeong, M. G., Kim, E.‐H., Hwang, E. S., Hong, J.‐H. TAZ stimulates liver regeneration through interleukin‐6–induced hepatocyte proliferation and inhibition of cell death after liver injury. FASEB J. 33, 5914–5923 (2019). http://www.fasebj.org

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SRC activates TAZ for intestinal tumorigenesis and regeneration

Cited by 26 publications

References 42 publications

Liver stiffness correlates with serum osteopontin and TAZ expression in human liver cirrhosis

Liver stiffness correlates with serum osteopontin and TAZ expression in human liver cirrhosis

YAP/TAZ Activation as a Target for Treating Metastatic Cancer

TAZ stimulates liver regeneration through interleukin‐6–induced hepatocyte proliferation and inhibition of cell death after liver injury

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