Common and Unique Transcription Signatures of YAP and TAZ in Gastric Cancer Cells

YAP and its paralog TAZ are the nuclear effectors of the Hippo tumour-suppressor pathway, and function as transcriptional co-activators to control gene expression in response to mechanical cues. To identify both common and unique transcriptional targets of YAP and TAZ in gastric cancer cells, we carried out RNA-sequencing analysis of overexpressed YAP or TAZ in the corresponding paralogous gene-knockouts (KOs), TAZ KO or YAP KO, respectively. Gene Ontology (GO) analysis of the YAP/TAZ-transcriptional targets revealed activation of genes involved in platelet biology and lipoprotein particle formation as targets that are common for both YAP and TAZ. However, the GO terms for cell-substrate junction were a unique function of YAP. Further, we found that YAP was indispensable for the gastric cancer cells to re-establish cell-substrate junctions on a rigid surface following prolonged culture on a soft substrate. Collectively, our study not only identifies common and unique transcriptional signatures of YAP and TAZ in gastric cancer cells but also reveals a dominant role for YAP over TAZ in the control of cell-substrate adhesion.

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Supervillin modulation of focal adhesions involving TRIP6/ZRP-1

The Journal of Cell Biology ◽

10.1083/jcb.200512051 ◽

2006 ◽

Vol 174 (3) ◽

pp. 447-458 ◽

Cited By ~ 36

Author(s):

Norio Takizawa ◽

Tara C. Smith ◽

Thomas Nebl ◽

Jessica L. Crowley ◽

Stephen J. Palmieri ◽

...

Keyword(s):

Focal Adhesions ◽

Stress Fibers ◽

Regulatory Sequence ◽

Interacting Protein ◽

Substrate Adhesion ◽

Lim Domains ◽

Cell Substrate ◽

Thyroid Receptor ◽

And Function ◽

Cell Substrate Adhesion

Cell–substrate contacts, called focal adhesions (FAs), are dynamic in rapidly moving cells. We show that supervillin (SV)—a peripheral membrane protein that binds myosin II and F-actin in such cells—negatively regulates stress fibers, FAs, and cell–substrate adhesion. The major FA regulatory sequence within SV (SV342-571) binds to the LIM domains of two proteins in the zyxin family, thyroid receptor–interacting protein 6 (TRIP6) and lipoma-preferred partner (LPP), but not to zyxin itself. SV and TRIP6 colocalize within large FAs, where TRIP6 may help recruit SV. RNAi-mediated decreases in either protein increase cell adhesion to fibronectin. TRIP6 partially rescues SV effects on stress fibers and FAs, apparently by mislocating SV away from FAs. Thus, SV interactions with TRIP6 at FAs promote loss of FA structure and function. SV and TRIP6 binding partners suggest several specific mechanisms through which the SV–TRIP6 interaction may regulate FA maturation and/or disassembly.

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Regulation of gastric carcinoma development in gastric adenoma/dysplasia by crebzf inhibition via miRNA-421.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.4_suppl.410 ◽

2020 ◽

Vol 38 (4_suppl) ◽

pp. 410-410 ◽

Cited By ~ 1

Author(s):

Yu Jin Kim ◽

Won Shik Kim ◽

Sang Woo Kim ◽

Woon Yong Jung

Keyword(s):

Gastric Cancer ◽

Cancer Cells ◽

Early Stage ◽

Gastric Adenoma ◽

Gastric Cancer Cells ◽

Gastric Cancer Cell Lines ◽

And Migration ◽

Gastric Cancer Patients ◽

And Function

410 Background: In our previous study, we identified three miRNAs (hsa-miR-421, hsa-miR-29b-1-5p, and hsa-miR-27b-5p) with two mRNAs (FBXO11 and CREBZF) that might play an important role in the development of gastric adenocarcinoma (GAC) from premalignant adenomas. However, the expression and function of these miRNAs have not been not well characterized. Methods: We investigated the roles of CREBZF and miRNAs as potential biomarkers for the progression of gastric cancer (GC) in low-/high-grade dysplasia and early gastric cancer patients using immunohistochemical staining and miRNA in situ hybridization. Considering that targets can modulate in GC, we analyzed the CREBZF expression in gastric cancer cell lines by RT-PCR and western blot analysis. Results: We observed lower expression of CREBZF with increasing miRNAs in the MKN-74 gastric cancer cells compared to that in SNU-NCC-19. Next, the role of CREBZF in MKN-74 gastric cancer cells was investigated via cell viability and migration assays by miRNA/anti-miRNA modulation. Furthermore, we found that hsa-miR-421/hsa-miR-29b-1-5p target CREBZF and might play an important role in the migration of MKN-74 cells. Conclusions: This study suggests that increased CREBZF by hsa-miR-421/hsa-miR-29b-1-5p inhibition may be important to prevent the progression of gastric cancer in its early stage.

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circCOL1A1 Promotes the Progression of Gastric Cancer Cells through Sponging miR-145 to Enhance RABL3 Expression

Journal of Immunology Research ◽

10.1155/2021/6724854 ◽

2021 ◽

Vol 2021 ◽

pp. 1-20

Author(s):

Yue Ma ◽

Yanyi Ren ◽

Huitao Wen ◽

Chengcheng Cui

Keyword(s):

Gastric Cancer ◽

Cancer Cells ◽

Cancer Cell ◽

Gastric Cancer Cell ◽

Circular Rna ◽

Migration And Invasion ◽

Gastric Cancer Cells ◽

Gastric Cancer Cell Lines ◽

Microrna Sponge ◽

And Function

Circular RNA has been reported to be a new noncoding RNA which plays important roles in tumor progression. One of the most common functions of circular RNA is to regulate microRNA expression by acting as a microRNA sponge. However, the circular RNA expression profile and function remain mostly unclear in gastric cancer. In the study, we explored the expression and function of circCOL1A1 (hsa_circ_0044556) in gastric cancer. We performed RT-PCR with divergent primers, mRNA stability assay, and RNase R digestion assay to characterize circCOL1A1 in gastric cancer cell lines. qRT-PCR was applied to detect the level of circCOL1A1 in both gastric cancer cell lines and tissues. Gain- and loss-of-function studies were carried out to detect the influence of circCOL1A1 on gastric cancer cells by performing CCK8, migration, and invasion assays. The regulation of the downstream genes was identified by qRT-PCR, western blot assay, dual luciferase assay, and RNA pull-down assay. The results showed that circCOL1A1 was highly expressed in both gastric cancer cells and tissues. Silence of circCOL1A1 inhibited the proliferation, migration, and invasion of gastric cancer cells. circCOL1A1 regulated the expression of miR-145 by acting as a microRNA sponge, and the influence of circCOL1A1 could be abrogated by miR-145 mimics. Our research shows that miR-145 plays its functions through targeting and regulating RABL3. Inhibition of circCOL1A1/miR-145/RABL3 could effectively suppress gastric cancer cell proliferation, migration, and invasion. circCOL1A1 also promote the transformation of M1 into M2 macrophage. Our study identified circCOL1A1 as a novel oncogenic circRNA and will provide more information for gastric cancer therapy.

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Ephrin-independent regulation of cell substrate adhesion by the EphB4 receptor

Biochemical Journal ◽

10.1042/bj20090014 ◽

2009 ◽

Vol 422 (3) ◽

pp. 433-442 ◽

Cited By ~ 45

Author(s):

Nicole K. Noren ◽

Nai-Ying Yang ◽

Morgan Silldorff ◽

Ravi Mutyala ◽

Elena B. Pasquale

Keyword(s):

Cancer Cells ◽

Tyrosine Kinases ◽

Single Amino Acid ◽

Cell Contact ◽

Eph Receptors ◽

Independent Manner ◽

Protein Levels ◽

Substrate Adhesion ◽

Cell Substrate ◽

Cell Substrate Adhesion

Receptor tyrosine kinases of the Eph family become tyrosine phosphorylated and initiate signalling events upon binding of their ligands, the ephrins. Eph receptors such as EphA2 and EphB4 are highly expressed but poorly tyrosine phosphorylated in many types of cancer cells, suggesting a limited interaction with ephrin ligands. Nevertheless, decreasing the expression of these receptors affects the malignant properties of cancer cells, suggesting that Eph receptors may influence cancer cells independently of ephrin stimulation. Ligand-independent activities of Eph receptors in cancer, however, have not been demonstrated. By using siRNA (small interfering RNA) to downregulate EphB4 in MCF7 and MDA-MB-435 cancer cells, we found that EphB4 inhibits integrin-mediated cell substrate adhesion, spreading and migration, and reduces β1-integrin protein levels. Low expression of the EphB4 preferred ligand, ephrin-B2, and minimal contact between cells in these assays suggest that cell contact-dependent stimulation of EphB4 by the transmembrane ephrin-B2 ligand does not play a role in these effects. Indeed, inhibitors of ephrin-B2 binding to endogenous EphB4 did not influence cell substrate adhesion. Increasing EphB4 expression by transient transfection inhibited cell substrate adhesion, and this effect was also independent of ephrin stimulation because it was not affected by single amino acid mutations in EphB4 that impair ephrin binding. The overexpressed EphB4 was tyrosine phosphorylated, and we found that EphB4 kinase activity is important for inhibition of integrin-mediated adhesion, although several EphB4 tyrosine phosphorylation sites are dispensable. These findings demonstrate that EphB4 can affect cancer cell behaviour in an ephrin-independent manner.

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Matrine inhibits the adhesion and migration of BCG823 gastric cancer cells by affecting the structure and function of the vasodilator-stimulated phosphoprotein (VASP)

Acta Pharmacologica Sinica ◽

10.1038/aps.2013.15 ◽

2013 ◽

Vol 34 (8) ◽

pp. 1084-1092 ◽

Cited By ~ 16

Author(s):

Jing-wei Zhang ◽

Ke Su ◽

Wen-tao Shi ◽

Ying Wang ◽

Peng-chao Hu ◽

...

Keyword(s):

Gastric Cancer ◽

Cancer Cells ◽

Structure And Function ◽

Gastric Cancer Cells ◽

And Migration ◽

And Function

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Myoferlin depletion elevates focal adhesion kinase and paxillin phosphorylation and enhances cell-matrix adhesion in breast cancer cells

AJP Cell Physiology ◽

10.1152/ajpcell.00276.2014 ◽

2015 ◽

Vol 308 (8) ◽

pp. C642-C649 ◽

Cited By ~ 11

Author(s):

B. N. Blackstone ◽

R. Li ◽

W. E. Ackerman ◽

S. N. Ghadiali ◽

H. M. Powell ◽

...

Keyword(s):

Breast Cancer ◽

Focal Adhesion Kinase ◽

Cancer Cells ◽

Breast Cancer Cell ◽

Focal Adhesion ◽

Breast Cancer Cells ◽

Focal Adhesions ◽

Substrate Adhesion ◽

Cell Substrate ◽

Cell Substrate Adhesion

Breast cancer is the second leading cause of malignant death among women. A crucial feature of metastatic cancers is their propensity to lose adhesion to the underlying basement membrane as they transition to a motile phenotype and invade surrounding tissue. Attachment to the extracellular matrix is mediated by a complex of adhesion proteins, including integrins, signaling molecules, actin and actin-binding proteins, and scaffolding proteins. Focal adhesion kinase (FAK) is pivotal for the organization of focal contacts and maturation into focal adhesions, and disruption of this process is a hallmark of early cancer invasive potential. Our recent work has revealed that myoferlin (MYOF) mediates breast tumor cell motility and invasive phenotype. In this study we demonstrate that noninvasive breast cancer cell lines exhibit increased cell-substrate adhesion and that silencing of MYOF using RNAi in the highly invasive human breast cancer cell line MDA-MB-231 also enhances cell-substrate adhesion. In addition, we detected elevated tyrosine phosphorylation of FAK (FAKY397) and paxillin (PAXY118), markers of focal adhesion protein activation. Morphometric analysis of PAX expression revealed that RNAi-mediated depletion of MYOF resulted in larger, more elongated focal adhesions, in contrast to cells transduced with a control virus (MDA-231LVC cells), which exhibited smaller focal contacts. Finally, MYOF silencing in MDA-MB-231 cells exhibited a more elaborate ventral cytoskeletal structure near focal adhesions, typified by pronounced actin stress fibers. These data support the hypothesis that MYOF regulates cell adhesions and cell-substrate adhesion strength and may account for the high degree of motility in invasive breast cancer cells.

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Zyxin-VASP interactions alter actin regulatory activity in zyxin-VASP complexes

Cellular & Molecular Biology Letters ◽

10.2478/s11658-012-0035-2 ◽

2013 ◽

Vol 18 (1) ◽

pp. 1-10 ◽

Cited By ~ 3

Author(s):

Jacob Grange ◽

James Moody ◽

Marc Ascione ◽

Marc Hansen

Keyword(s):

Actin Dynamics ◽

Actin Assembly ◽

Regulatory Activity ◽

Substrate Adhesion ◽

Lim Domains ◽

Individual Interaction ◽

Cell Substrate ◽

And Function ◽

Cell Substrate Adhesion ◽

Cell Cell

AbstractCell-cell and cell-substrate adhesions are sites of dramatic actin rearrangements and where actin-membrane connections are tightly regulated. Zyxin-VASP complexes localize to sites of cell-cell and cell-substrate adhesion and function to regulate actin dynamics and actin-membrane connections at these sites. To accomplish these functions, zyxin recruits VASP to cellular sites via proline-rich binding sites near zyxin’s amino terminus. While the prevailing thought has been that zyxin simply acts as a scaffold protein for VASP binding, the identification of a LIM domain-VASP interaction could complicate this view. Here we assess how zyxin-VASP binding through both the proline rich motifs and the LIM domains alters specific VASP functions. We find that neither individual interaction alters VASP’s actin regulatory activities. In contrast, however, we find that full-length zyxin dramatically reduces VASPmediated actin bundling and actin assembly. Taken together, these results suggest a model where zyxin-VASP complexes occur in complex organizations with suppressed actin regulatory activity.

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