Hyaluronic acid-CD44 interactions promote BMP4/7-dependent Id1/3 expression in melanoma cells

Wu, Ruolin; Sedlmeier, Georg; Kyjacová, Lenka; Schmaus, Anja; Philipp, Julia; Thiele, Wilko; Garvalov, Boyan K.; Sleeman, Jonathan

doi:10.1038/s41598-018-33337-7

Cited by 27 publications

(21 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Visualization of pericellular HA using the HABP probe revealed an abundant pericellular coat associated with IPF MPCs. Pericellular HA-CD44 interactions have been shown to regulate cancer cell tumorgenicity (59). We show that overexpression of HAS2 in IPF MPCs augments HA release from the cell, promotes S100A4 nuclear accumulation in a CD44-dependent manner, and increases IPF MPC self-renewal.…”

Section: Discussionmentioning

confidence: 72%

Hyaluronan/CD44 axis regulates S100A4-mediated mesenchymal progenitor cell fibrogenicity in idiopathic pulmonary fibrosis

Xia

Herrera

Smith

et al. 2021

American Journal of Physiology-Lung Cellular and Molecular Phys

View full text Add to dashboard Cite

Despite modest improvement in patient outcomes from recent advances in pharmacotherapy targeting fibrogenic signaling pathways, IPF remains a major unsolved clinical problem. One reason for this is that available anti-fibrotic agents slow but do not arrest fibrotic progression. To arrest fibrotic progression, its obligatory drivers need to be identified. We previously discovered that fibrogenic mesenchymal progenitor cells (MPCs) are key drivers of fibrotic progression in IPF, serving as cells-of-origin for disease-mediating myofibroblasts. IPF MPCs have high levels of nuclear S100A4, which interacts with the proteasome to promote p53 degradation and self-renewal. However, the mechanism underlying S100A4 accumulation in the nucleus of IPF MPCs remains unknown. Here we show that hyaluronan (HA) is present in the fibroblastic focus together with CD44 expressing MPCs and that ligation of CD44 by HA triggers S100A4 nuclear translocation to support IPF MPC self-renewal. The mechanism involves HA-mediated formation of a CD44/S100A4/transportin1 complex, which promotes S100A4 nuclear import. In a humanized mouse model of pulmonary fibrosis, IPF MPC fibrogenicity was significantly attenuated by: i) knockdown of CD44; or ii) introduction of a S100A4 mutant construct which prevents S100A4 nuclear import. These data indicate that signaling through the HA/CD44/S100A4 axis is an integral component of IPF MPC fibrogenicity.

show abstract

Section: Discussionmentioning

confidence: 72%

Hyaluronan/CD44 axis regulates S100A4-mediated mesenchymal progenitor cell fibrogenicity in idiopathic pulmonary fibrosis

Xia

Herrera

Smith

et al. 2021

American Journal of Physiology-Lung Cellular and Molecular Phys

View full text Add to dashboard Cite

show abstract

“…In our study, the status of ID1 expression in HCC specimens was not completely consisted with the status of BMP9 expression, and ID1 regulated EpCAM expression even in the absence of BMP9. These findings imply that other factors may be involved in the activation of ID1 expression [27,28]. In addition, c-Myc also regulates ID1 by a positive feedback-loop regulatory mechanism [29].…”

Section: Accepted Articlementioning

confidence: 92%

BMP9‐ID1 signaling promotes EpCAM‐positive cancer stem cell properties in hepatocellular carcinoma

et al. 2021

View full text Add to dashboard Cite

The malignant nature of hepatocellular carcinoma (HCC) is closely related to the presence of cancer stem cells (CSCs). Bone morphologic protein 9 (BMP9), a member of the transforming growth factor-beta (TGF-β) superfamily, was recently reported to be involved in liver diseases including cancer. We aimed to elucidate the role of BMP9 signaling in HCC-CSC properties and to assess the therapeutic effect of BMP receptor inhibitors in HCC. We have identified that high BMP9 expression in tumor tissues or serum from patients with HCC leads to poorer outcome. BMP9 promoted CSC properties in epithelial cell adhesion molecule (EpCAM)-positive HCC subtype via enhancing inhibitor of DNA-binding protein 1 (ID1) expression in vitro. Additionally, ID1 knockdown significantly repressed BMP9-promoted HCC-CSC properties by suppressing Wnt/β-catenin signaling. Interestingly, cells treated with BMP receptor inhibitors K02288 and LDN-212854 blocked HCC-CSC activation by inhibiting BMP9-ID1 signaling, in contrast to cells treated with the TGF-β receptor inhibitor galunisertib. . Treatment with LDN-212854 suppressed HCC tumor growth by repressing ID1 and EpCAM in vivo. Our study demonstrates the pivotal role of BMP9-ID1 signaling in promoting HCC-CSC properties and the therapeutic potential of BMP receptor inhibitors in treating EpCAM-positive HCC. Therefore, targetingBMP9-ID1 signaling could offer novel therapeutic options for patients with malignant HCC.

show abstract

“…The inhibition of HA synthesis/signaling or the depletion of HA in tumor stroma may be a promising therapeutic approach to fight against PDAC progression (112). HA was also reported to facilitate cell proliferation and invasiveness in malignant pleural mesothelioma (163) and in melanoma (164) and may be used as a biomarker for early diagnosis and management of these diseases (163)(164)(165).…”

Section: Proteoglycansmentioning

confidence: 99%

Tumor Microenvironment: Extracellular Matrix Alterations Influence Tumor Progression

et al. 2020

View full text Add to dashboard Cite

The tumor microenvironment (TME) is composed of various cell types embedded in an altered extracellular matrix (ECM). ECM not only serves as a support for tumor cell but also regulates cell-cell or cell-matrix cross-talks. Alterations in ECM may be induced by hypoxia and acidosis, by oxygen free radicals generated by infiltrating inflammatory cells or by tumor-or stromal cell-secreted proteases. A poorer diagnosis for patients is often associated with ECM alterations. Tumor ECM proteome, also named cancer matrisome, is strongly altered, and different ECM protein signatures may be defined to serve as prognostic biomarkers. Collagen network reorganization facilitates tumor cell invasion. Proteoglycan expression and location are modified in the TME and affect cell invasion and metastatic dissemination. ECM macromolecule degradation by proteases may induce the release of angiogenic growth factors but also the release of proteoglycan-derived or ECM protein fragments, named matrikines or matricryptins. This review will focus on current knowledge and new insights in ECM alterations, degradation, and reticulation through cross-linking enzymes and on the role of ECM fragments in the control of cancer progression and their potential use as biomarkers in cancer diagnosis and prognosis.

show abstract

Hyaluronic acid-CD44 interactions promote BMP4/7-dependent Id1/3 expression in melanoma cells

Cited by 27 publications

References 45 publications

Hyaluronan/CD44 axis regulates S100A4-mediated mesenchymal progenitor cell fibrogenicity in idiopathic pulmonary fibrosis

Hyaluronan/CD44 axis regulates S100A4-mediated mesenchymal progenitor cell fibrogenicity in idiopathic pulmonary fibrosis

BMP9‐ID1 signaling promotes EpCAM‐positive cancer stem cell properties in hepatocellular carcinoma

Tumor Microenvironment: Extracellular Matrix Alterations Influence Tumor Progression

Contact Info

Product

Resources

About