Active YAP promotes pancreatic cancer cell motility, invasion and tumorigenesis in a mitotic phosphorylation-dependent manner through LPAR3

Yang, Shuping; Zhang, Lin; Purohit, Vinee; Shukla, Surendra K.; Chen, Xingcheng; Yu, Fang; Fu, Kai; Chen, Yuanhong; Solheim, Joyce C.; Singh, Pankaj K.; Song, Wei; Dong, Jixin

doi:10.18632/oncotarget.5935

Cited by 89 publications

(82 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Excluding Sema6d , these are novel upregulated genes in T cells (42–45). Both Sema6d and the E-cadherin gene were also upregulated relative to peripheral spleen CD8 T cells (both CD103 − and CD103 + ), supporting the possibility that these genes are unique determinants of residency for the brain CD103 + population in our model (Figure S5 in Supplementary Material).…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

CD103+ CD8 T Cells in the Toxoplasma-Infected Brain Exhibit a Tissue-Resident Memory Transcriptional Profile

et al. 2017

View full text Add to dashboard Cite

During chronic infection, memory T cells acquire a unique phenotype and become dependent on different survival signals than those needed for memory T cells generated during an acute infection. The distinction between the role of effector and memory T cells in an environment of persistent antigen remains unclear. Here, in the context of chronic Toxoplasma gondii infection, we demonstrate that a population of CD8 T cells exhibiting a tissue-resident memory (TRM) phenotype accumulates within the brain. We show that this population is distributed throughout the brain in both parenchymal and extraparenchymal spaces. Furthermore, this population is transcriptionally distinct and exhibits a transcriptional signature consistent with the TRM observed in acute viral infections. Finally, we establish that the CD103+ TRM population has an intrinsic capacity to produce both IFN-γ and TNF-α, cytokines critical for parasite control within the central nervous system (CNS). The contribution of this population to pro-inflammatory cytokine production suggests an important role for TRM in protective and ongoing immune responses in the infected CNS.Accession number: GSE95105

show abstract

Section: Resultsmentioning

confidence: 99%

“…These include the GPCR Lpar3 and the guanidine exchange factor Swap70 , which are upregulated (42, 45). Swap70 expression, although typically associated with B cells, has also been shown to initiate membrane ruffling in fibroblasts (42).…”

Section: Discussionmentioning

confidence: 99%

CD103+ CD8 T Cells in the Toxoplasma-Infected Brain Exhibit a Tissue-Resident Memory Transcriptional Profile

et al. 2017

View full text Add to dashboard Cite

show abstract

“…However, the physiological outcomes of these phosphorylation events are rather perplexing, as their effects on cell growth and migration are not entirely consistent among reports from different groups. While some studies show that CDK1-mediated YAP phosphorylation during the G2-M phase may promote neoplastic transformation via enhancing cell migration and invasion (Yang et al 2013(Yang et al , 2015c, others suggest that anti-tubulin drugs require YAP phosphorylation by CDK1 to induce cancer cell death ). This inconsistency may be due to different experimental conditions that differentially affect the coordination between CDK1 and LATS1/2 in the modulation of YAP activity.…”

Section: Cell Cyclementioning

confidence: 99%

Mechanisms of Hippo pathway regulation

2016

View full text Add to dashboard Cite

The Hippo pathway was initially identified in Drosophila melanogaster screens for tissue growth two decades ago and has been a subject extensively studied in both Drosophila and mammals in the last several years. The core of the Hippo pathway consists of a kinase cascade, transcription coactivators, and DNA-binding partners. Recent studies have expanded the Hippo pathway as a complex signaling network with >30 components. This pathway is regulated by intrinsic cell machineries, such as cell–cell contact, cell polarity, and actin cytoskeleton, as well as a wide range of signals, including cellular energy status, mechanical cues, and hormonal signals that act through G-protein-coupled receptors. The major functions of the Hippo pathway have been defined to restrict tissue growth in adults and modulate cell proliferation, differentiation, and migration in developing organs. Furthermore, dysregulation of the Hippo pathway leads to aberrant cell growth and neoplasia. In this review, we focus on recent developments in our understanding of the molecular actions of the core Hippo kinase cascade and discuss key open questions in the regulation and function of the Hippo pathway.

show abstract

“…MOB2 directly phosphorylates YAP, and the inactivation of YAP by cytoplasmic retention is linked with the regulation of cell motility and proliferation (12,(16)(17)(18)(22)(23)(24), thereby establishing an association between NDR1/2 kinases with the Hippo signaling pathway on a cellular level. A previous study by the present authors has demonstrated that MOB2 serves an inhibitory role in the motility of the HCC cell lines SMMC-7721 and HepG2 (8).…”

Section: Discussionmentioning

confidence: 99%

Monopolar spindle-one-binder protein 2 regulates the activity of large tumor suppressor/yes-associated protein to inhibit the motility of SMMC-7721 hepatocellular carcinoma cells

Zhang

Shen

et al. 2018

Oncol Lett

View full text Add to dashboard Cite

Abstract. Accumulating evidence implicates monopolar spindle-one-binder protein (MOB)2 as an inhibitor of nuclear-Dbf2-related kinase (NDR) by competing with MOB1 for interaction with NDR1/2. NDR/large tumor suppressor (LATS) kinases may function similarly to yes-associated protein (YAP) kinases and be considered as members of the Hippo core cassette. MOB2 appears to serve roles in cell survival, cell cycle progression, responses to DNA damage and cell motility. However, the underlying mechanisms involved remain unclarified. In the present study, it was demonstrated that the knockout of MOB2 by clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR associated protein 9 promoted migration and invasion, induced phosphorylation of NDR1/2 and decreased phosphorylation of YAP in SMMC-7721 cells when compared with the blank vector-transduced cells. By contrast, the overexpression of MOB2 resulted in the opposite results. Mechanistically, MOB2 regulated the alternative interaction of MOB1 with NDR1/2 and LATS1, which resulted in increased phosphorylation of LATS1 and MOB1 and thereby led to the inactivation of YAP and consequently inhibition of cell motility. The results of the present study provide evidence of MOB2 serving a positive role in LATS/YAP activation by activating the Hippo signaling pathway.

show abstract

Active YAP promotes pancreatic cancer cell motility, invasion and tumorigenesis in a mitotic phosphorylation-dependent manner through LPAR3

Abstract: The transcriptional co-activator Yes-associated protein, YAP, is a main effector

Cited by 89 publications

References 43 publications

CD103+ CD8 T Cells in the Toxoplasma-Infected Brain Exhibit a Tissue-Resident Memory Transcriptional Profile

CD103+ CD8 T Cells in the Toxoplasma-Infected Brain Exhibit a Tissue-Resident Memory Transcriptional Profile

Mechanisms of Hippo pathway regulation

Monopolar spindle-one-binder protein 2 regulates the activity of large tumor suppressor/yes-associated protein to inhibit the motility of SMMC-7721 hepatocellular carcinoma cells

Contact Info

Product

Resources

About