Targeting of syndecan‐1 by microRNA miR‐10b promotes breast cancer cell motility and invasiveness <i>via</i> a Rho‐GTPase‐ and E‐cadherin‐dependent mechanism

Ibrahim, Sherif; Yip, George; Stock, Christian; Pan, Junwei; Neubauer, Claudia; Poeter, Michaela; Pupjalis, Danute; Koo, Chuay-Yeng; Kelsch, Reinhard; Schüle, Roland; Rescher, Ursula; Kiesel, L.; Götte, Martin

doi:10.1002/ijc.27629

Cited by 150 publications

(181 citation statements)

References 46 publications

(107 reference statements)

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“…Tumor invasion and metastasis is a complex and multistep process: miR-10b may play different roles via different targets [18,22,24,25]. Previous studies indicated that miR-10b restrained Tiam1 by translational inhibition, in which the 3 0 UTR miR-10b-binding site is crucial [26].…”

Section: Discussionmentioning

confidence: 99%

DNA methylation downregulated mir-10b acts as a tumor suppressor in gastric cancer

et al. 2014

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Background MicroRNAs act as tumor suppressors or oncogenes. The pathological roles of miRNAs in gastric tumorigenesis are largely unknown. Although miR-10b was identified as an miRNA deregulator expressed in gastric cancer (GC), there also exists some debate on whether miR-10b is acting as tumor suppressor or oncogene in GC. Methods Quantitative RT-PCR was employed to investigate the level of miR-10b in GC tissues and matched adjacent normal tissues (n = 100). In vitro cell proliferation, apoptosis assays, cell migration, and invasion assays were performed to elucidate the biological effects of miR10b. Because silencing of miRNA by promoter CpG island methylation may be an important mechanism in tumorigenesis, GC cells were treated with 5-aza-2 0 -deoxycytidine and trichostatin A, and expression changes of miR-10b were subsequently examined by quantitative RT-PCR. Furthermore, the methylation status of the CpG island upstream of miR-10b was analyzed by methylation-specific PCR in GC tissues (n = 29). Results We showed here that miR-10b was significantly downregulated in GC cell lines and tissues as demonstrated by quantitative real-time PCR. Overexpression of miR-10b in MGC-803 and HGC-27 dramatically suppressed cell proliferation, migration, invasion, and induced apoptosis. Moreover, we demonstrated that T-cell lymphoma invasion and metastasis (Tiam1) was a target of miR-10b. Furthermore, 5-aza-2 0 -deoxycytidine and trichostain A increased miR-10b expression, and the methylation level was high in the CpG islands upstream of miR-10b gene. Conclusions Taken together, these findings suggest that miR-10b may function as a novel tumor suppressor and is partially silenced by DNA hypermethylation in GC.

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Section: Discussionmentioning

confidence: 99%

DNA methylation downregulated mir-10b acts as a tumor suppressor in gastric cancer

et al. 2014

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“…As we also observed syndecan-1-dependent wound closure in the presence of mitomycin blocking cell proliferation, we conclude that syndecan-1 is critical for migration of cells into the wounded area. Several signaling pathways that are implicated in cell proliferation and migration including p38, Akt, Rho GTPase and FAK are modulated by knockdown or overexpression of syndecan-1 [20,40,41]. However, the effects appear to be cell-type dependent.…”

Section: Discussionmentioning

confidence: 98%

A transmembrane C-terminal fragment of syndecan-1 is generated by the metalloproteinase ADAM17 and promotes lung epithelial tumor cell migration and lung metastasis formation

Pasqualon

Pruessmeyer

Weidenfeld

et al. 2015

Cell. Mol. Life Sci.

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Syndecan-1 is a heparan sulfate proteoglycan expressed by endothelial and epithelial cells and involved in wound healing and tumor growth. Surface-expressed syndecan-1 undergoes proteolytic shedding leading to the release of the soluble N-terminal ectodomain from a transmembrane C-terminal fragment (tCTF). We show that the disintegrin and metalloproteinase (ADAM) 17 generates a syndecan-1 tCTF, which can then undergo further intra-membrane proteolysis by γ-secretase. Scratch-induced wound closure of cultured lung epithelial A549 tumor cells associates with increased syndecan-1 cleavage as evidenced by the release of shed syndecan-1 ectodomain and enhanced generation of the tCTF. Both wound closure and the associated syndecan-1 shedding can be suppressed by inhibition of ADAM family proteases. Cell proliferation, migration and invasion into matrigel as well as several signaling pathways implicated in these responses are suppressed by silencing of syndecan-1. These defects of syndecan-1 deficient cells can be overcome by overexpression of syndecan-1 tCTF or a corresponding tCTF of syndecan-4 but not by overexpression of a tCTF lacking the transmembrane domain. Finally, lung metastasis formation of A549 cells in SCID mice was found to be dependent on syndecan-1, and the presence of syndecan-1 tCTF was sufficient for this activity. Thus, the syndecan-1 tCTF by itself is capable of mediating critical syndecan-1-dependent functions in cell proliferation, migration, invasion and metastasis formation and therefore can replace full length syndecan-1 in the situation of increased syndecan-1 shedding during cell migration and tumor formation.

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“…Other potentially critical factors that may be relevant in TNBC include the interplay between EGFR and insulin-like growth factor receptor signaling systems and production of cell surface effectors such as the subclass of heparin sulfate proteoglycans known as syndecans (52)(53)(54)(55)(56). Understanding how these different factors are integrated to drive metastatic progression will provide the Somewhat surprisingly, our data also appear to exclude a role for autocrine IL-6 because EMT programs fail to diminish the ability of NME cells to activate STAT3 in response to exogenous IL-6.…”

Section: Figure 4 Emt Inhibits Egfr-dependent Stat3 Signalingmentioning

confidence: 99%

Epithelial to Mesenchymal Transition Promotes Breast Cancer Progression via a Fibronectin-dependent STAT3 Signaling Pathway

Balanis

Wendt²,

Schiemann³

et al. 2013

Journal of Biological Chemistry

122

113

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Background: Cells perceive their environment through soluble growth factors and in response to extracellular matrix. Results: STAT3 signaling can be activated by multiple pathways during breast cancer progression. Conclusion: Fibronectin:STAT3 signaling promotes three-dimensional outgrowth of breast cancer cells. Significance: This study demonstrates a novel mechanism by which STAT3 becomes activated by the extracellular matrix independent of the canonical EGF receptor signaling network.

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Targeting of syndecan‐1 by microRNA miR‐10b promotes breast cancer cell motility and invasiveness via a Rho‐GTPase‐ and E‐cadherin‐dependent mechanism

Cited by 150 publications

References 46 publications

DNA methylation downregulated mir-10b acts as a tumor suppressor in gastric cancer

DNA methylation downregulated mir-10b acts as a tumor suppressor in gastric cancer

A transmembrane C-terminal fragment of syndecan-1 is generated by the metalloproteinase ADAM17 and promotes lung epithelial tumor cell migration and lung metastasis formation

Epithelial to Mesenchymal Transition Promotes Breast Cancer Progression via a Fibronectin-dependent STAT3 Signaling Pathway

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