TAZ Mediates Lysophosphatidic Acid-Induced Migration and Proliferation of Epithelial Ovarian Cancer Cells

Jeong, Geun Ok; Shin, Sang Hun; Seo, Eun Jin; Kwon, Yang Woo; Heo, Soon Chul; Kim, Ki-Hyung; Yoon, Man Soo; Suh, Dong‐Soo; Kim, Jae Ho

doi:10.1159/000354434

Cited by 51 publications

(40 citation statements)

References 33 publications

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“…67 In recent years, emerging evidences showed that LPA also stimulated ovarian cancer cell proliferation and motility via MAPK, CXCL12-CXCR4 axis, TAZ (transcriptional co-activator with PDZ binding motif), and its downstream signaling pathways. 68 Sphingosine kinases 1 (SphK1), one kinase of S1P production, is overexpressed in many types of cancers. It has been reported that crosstalk between LPA/LPA1 and epidermal growth factor receptors (EGFRs) mediated the upregulation of SphK1 to promote cell proliferation and motility in gastric cancer cells and squamous cell carcinoma cell lines of the head and neck.…”

Section: Expression Of Atx/lpa Axis In Cancermentioning

confidence: 99%

“…The coadministration of inhibitor to the ATX/LPA axis with sunitinib would prolong the sensitivity of renal cell carcinoma to sunitinib in the xenograft model. 68 A recent research has shown that LPA signaling increased Nrf2 transcription factor stability and nuclear localization, and further increased transcription of multidrug-resistant transporters and antioxidant genes, which protected cells from chemotherapy-induced death. 95 In recent years, the role of the ATX/LPA axis in cancer resistance to radiotherapy has also emerged.…”

Section: Expression Of Atx/lpa Axis In Cancermentioning

confidence: 99%

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The critical role and potential target of the autotaxin/lysophosphatidate axis in pancreatic cancer

et al. 2017

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Autotaxin, an ecto-lysophospholipase D encoded by the human ENNP2 gene, is expressed in multiple tissues, and participates in numerous critical physiologic and pathologic processes including inflammation, pain, obesity, embryo development, and cancer via the generation of the bioactive lipid lysophosphatidate. Overwhelming evidences indicate that the autotaxin/lysophosphatidate signaling axis serves key roles in the numerous processes central to tumorigenesis and progression, including proliferation, survival, migration, invasion, metastasis, cancer stem cell, tumor microenvironment, and treatment resistance by interacting with a series of at least six G-protein-coupled receptors (LPAR1-6). This review provides an overview of the autotaxin/lysophosphatidate axis and collates current knowledge regarding its specific role in pancreatic cancer. With a deeper understanding of the critical role of the autotaxin/lysophosphatidate axis in pancreatic cancer, targeting autotaxin or lysophosphatidate receptor may be a potential and promising strategy for cancer therapy.

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Section: Expression Of Atx/lpa Axis In Cancermentioning

confidence: 99%

Section: Expression Of Atx/lpa Axis In Cancermentioning

confidence: 99%

The critical role and potential target of the autotaxin/lysophosphatidate axis in pancreatic cancer

et al. 2017

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“…In ovarian CSCs, YAP promotes ovarian CSC tumorigenesis and regulates CSC self-renewal and differentiation [26,27]. The transcriptional co-activator with PDZ-binding motif (TAZ) is a transcriptional effector of the Hippo signaling cascade and regulates cell proliferation and tumorigenesis [21,28,29]. In addition, previous studies have shown that YAP acts as an oncogene in a subtype of breast CSCs and lung CSCs, thus serving as a good target for molecular therapies against cancers.…”

Section: Introductionmentioning

confidence: 99%

Ovarian Germline Stem Cells (OGSCs) and the Hippo Signaling Pathway Association with Physiological and Pathological Ovarian Aging in Mice

Zhou

Zheng

et al. 2015

Cell Physiol Biochem

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Background: The Hippo signaling pathway plays fundamental roles in stem cell maintenance in a variety of tissues and has thus implications for stem cell biology. Key components of this recently discovered pathway have been shown to be associated with primordial follicle activation. However, whether the Hippo signaling pathway plays a role in the development of Ovarian Germline Stem Cells (OGSCs) during physiological and pathological ovarian aging in mice is unknown. Methods: Mice at the age of 7 days (7D), or of 2, 10, or 20 months (2M, 10M, 20M) and mice at 2M treated with TPT and CY/BUS drugs were selected as physiological and pathological ovarian aging models, respectively. Immunohistochemistry was used to assess the development of follicles, and the co-localization of genes characteristic of OGSCs with MST1, LATS2 and YAP1 was assessed by immunofluorescence, western blotting and real-time PCR methods. Results: The Hippo signal pathway and MVH/OCT4 genes were co-expressed in the mouse ovarian cortex. The level and co-localization of LATS2, MST1, MVH, and OCT4 were significantly decreased with increased age, but YAP1 was more prevalent in the mouse ovarian cortex of 2M mice than 7D mice and was not observed in 20M mice. Furthermore, YAP1, MVH, and OCT4 were gradually decreased after TPT and CY/BUS treatment, and LATS2 mRNA and protein up-regulation persisted in TPT- and CY/BUS-treated mice. However, the expression of MST1 was lower in the TPT and CY/BUS groups compared with the control group. In addition, pYAP1 protein showed the highest expression in the ovarian cortexes of 7D mice compared with 20M mice, and the value of pYAP1/YAP1 decreased from 7D to 20M. Moreover, pYAP1 decreased in the TPT- and CY/BUS-treated groups, but the value of pYAP1/YAP1 increased in these groups. Conclusion: Taken together, our results show that the Hippo signaling pathway is associated with the changes that take place in OGSCs during physiological and pathological ovarian aging in mice. Thus, the Hippo signaling pathway may be involved in the development schedule of OGSCs.

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“…Two subsequent studies further confirmed the stimulation of YAP/ TAZ by LPA in ovarian cancer cells [39,40]. Cai and Xu [39] showed that LPA induced YAP dephosphorylation and nuclear localization in dose and time-dependent manner in several ovarian cancer cell lines.…”

Section: Introductionmentioning

confidence: 76%

“…Finally, they observed that the phosphorylation level of YAP was reduced in epithelia ovarian cancer (EOC) specimens compared with normal or benign ovarian tissues, supporting that the phosphorylated YAP could serve as a biomarker for EOC [39]. Jeong et al [40] also found that the activation of TAZ by LPA treatment could be blocked by specific LPA receptor inhibitor Ki16425 or siRNA target LPA1, and TAZ is required for LPA-induced ovarian cancer cell migration. These two studies strengthened the potential role of LPA in regulating YAP/TAZ in cancer cells and indicated that this axis may play crucial role in numerous cancer types.…”

Section: Introductionmentioning

confidence: 94%

G protein-coupled receptors: bridging the gap from the extracellular signals to the Hippo pathway

Zhou¹,

Wang²,

Huang³

et al. 2015

ABBS

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The Hippo pathway is crucial in organ size control, whereas its dysregulation contributes to organ degeneration or tumorigenesis. The kinase cascade of MST1/2 and LATS1/2 and the coupling transcription co-activators YAP/TAZ represent the core components of the Hippo pathway. Extensive studies have identified a number of upstream regulators of the Hippo pathway, including contact inhibition, mechanic stress, extracellular matrix stiffness, cytoskeletal rearrangement, and some molecules of cell polarity and cell junction. However, how the diffuse extracellular signals regulate the Hippo pathway puzzles the researchers for a long time. Unexpectedly, recent elegant studies demonstrated that stimulation of some G protein-coupled receptors (GPCRs), such as lysophosphatidic acid receptor, sphingosine-1-phosphate receptor, and the protease activated receptor PAR1, causes potent YAP/ TAZ dephosphorylation and activation by promoting actin cytoskeleton assemble. In this review, we briefly describe the components of the Hippo pathway and focus on the recent progress with respect to the regulation of the Hippo pathway by GPCRs and G proteins in cancer cells. In addition, we also discuss the potential therapeutic roles targeting the Hippo pathway in human cancers.

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TAZ Mediates Lysophosphatidic Acid-Induced Migration and Proliferation of Epithelial Ovarian Cancer Cells

Cited by 51 publications

References 33 publications

The critical role and potential target of the autotaxin/lysophosphatidate axis in pancreatic cancer

The critical role and potential target of the autotaxin/lysophosphatidate axis in pancreatic cancer

Ovarian Germline Stem Cells (OGSCs) and the Hippo Signaling Pathway Association with Physiological and Pathological Ovarian Aging in Mice

G protein-coupled receptors: bridging the gap from the extracellular signals to the Hippo pathway

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