Heregulin-mediated ErbB2-ERK Signaling Activates Hyaluronan Synthases Leading to CD44-dependent Ovarian Tumor Cell Growth and Migration

Bourguignon, Lilly Y.W.; Gilad, Eli; Peyrollier, Karine

doi:10.1074/jbc.m610054200

Cited by 139 publications

(133 citation statements)

References 87 publications

(133 reference statements)

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“…The fact that filamin (a 280-kDa actin-binding protein) is known to bind the p21-binding domain (PBD) of PAK1 (aa52-132) forms a complex with PAK1 during HA/ CD44-mediated extracellular signal-regulated kinase (ERK) signaling, suggests that a PAK1-filamin interaction could contribute significantly to cytoskeletal regulation in tumor progression. These findings are consistent with the previous findings that PAK1 activation is closely involved in filamin-mediated motility [96].…”

Section: Ha/cd44-mediated Cdc42 Signalingsupporting

confidence: 94%

“…PAK1 is known to be involved in cortical actin remodeling induced by RhoGTPases such as Rac or Cdc42, and plays a significant role in a variety of biological activities [95]. A recent study indicates that HA/ CD44-mediated signaling stimulates both Cdc42-CD44 association and PAK1 phosphorylation [96]. The fact that filamin (a 280-kDa actin-binding protein) is known to bind the p21-binding domain (PBD) of PAK1 (aa52-132) forms a complex with PAK1 during HA/ CD44-mediated extracellular signal-regulated kinase (ERK) signaling, suggests that a PAK1-filamin interaction could contribute significantly to cytoskeletal regulation in tumor progression.…”

Section: Ha/cd44-mediated Cdc42 Signalingmentioning

confidence: 99%

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Hyaluronan-mediated CD44 activation of RhoGTPase signaling and cytoskeleton function promotes tumor progression

Bourguignon

2008

Seminars in Cancer Biology

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267

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Hyaluronan (HA), a major component of the extracellular matrix (ECM), is enriched in many types of tumors. In cancer patients HA concentrations are usually higher in malignant tumors than in corresponding benign or normal tissues, and in some tumor types the level of HA is predictive of malignancy. HA is often bound to CD44 isoforms which are ubiquitous, abundant, and functionally important cell surface receptors. This article reviews the current evidence for HA/CD44-mediated activation of the ankyrin-based cytoskeleton and RhoGTPase signaling during tumor progression. A special focus is placed on the role of HA-mediated CD44 interaction with unique downstream effectors (e.g., the cytoskeletal protein, ankyrin and/or various GTPases (e.g., RhoA, Rac1 and Cdc42)) in coordinating intracellular signaling pathways (e.g., Ca 2+ mobilization, Rho signaling, PI3 kinase-AKT activation, NHE1-mediated cellular acidification, transcriptional upregulation and cytoskeletal function) and generating the concomitant onset of tumor cell activities (e.g., tumor cell adhesion, growth, survival, migration and invasion) and tumor progression. I believe this information will provide valuable new insights into poorly understood aspects of solid tumor malignancy. Furthermore, the new knowledge concerning HA/CD44-mediated oncogenic signaling events will have potentially important clinical utility, and could establish CD44 and its associated signaling molecules as important tumor markers for the early detection and evaluation of oncogenic potential. It could also serve as ground work for the future development of new drug targets to inhibit HA/ CD44-mediated tumor metastasis and cancer progression.

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Section: Ha/cd44-mediated Cdc42 Signalingsupporting

confidence: 94%

Section: Ha/cd44-mediated Cdc42 Signalingmentioning

confidence: 99%

Hyaluronan-mediated CD44 activation of RhoGTPase signaling and cytoskeleton function promotes tumor progression

Bourguignon

2008

Seminars in Cancer Biology

Self Cite

267

279

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“…Dysregulation of putative target genes within these lists have been described in ovarian cancer. [74][75][76][77][78][79][80][81][82][83][84][85][86][87][88] E-cadherin and acatenin, components of the cadherin pathway, have previously been found to be dysregulated in metatstatic ovarian carcinoma and serous effusions. [79][80][81] Polymorphisms in cyclin D2 and protein kinase C isoform expression have been linked with prognosis in ovarian carcinoma patients.…”

Section: Discussionmentioning

confidence: 99%

Potentially important microRNA cluster on chromosome 17p13.1 in primary peritoneal carcinoma

et al. 2009

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MicroRNAs are a group of small non-coding RNAs approximately 22 nucleotides in length. Recent work has shown differential expression of mature microRNAs in human cancers. We characterized the alteration in expression of a select group of microRNAs in primary peritoneal carcinoma relative to matched cases of ovarian serous carcinoma. MicroRNA expression was analysed using semi-quantitative stem-loop RT-PCR on a set of 34 formalin-fixed paraffin-embedded samples. Protein expression of p53 and bcl-2 was quantified in the corresponding tissue microarray. We provide definitive evidence that there is downregulation of a select group of microRNAs in tumours meeting Gynaecological Oncology Group criteria for primary peritoneal carcinoma relative to ovarian serous carcinoma. Specifically, we show decreased p53 expression and downregulation of miR-195 and miR-497 from the microRNA cluster site at chromosome 17p13.1 in primary peritoneal carcinoma relative to ovarian serous carcinoma. miR-195 and miR-497 may have potential roles as tumour-suppressor genes in primary peritoneal tumourigenesis.

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“…Expression of V3 Attenuates EGFR-and NFB-dependent Signaling Pathways-Hyaluronan synthesis is regulated by a number of signaling pathways, including the EGFR-PI3K/ERK signaling network (33)(34)(35)(36)(37). Moreover, hyaluronan synthases have NFB binding regions in their promoters that are regulated by NFB agonists, such as interleukin 1␤ (IL-1␤) and tumor necrosis factor ␣ (TNF␣) (25, 38 -40).…”

Section: Enhanced Tropoelastin and Fibulin 5 Mrna Expression In V3-exmentioning

confidence: 99%

“…Hyaluronan synthesis is regulated by a number of pathways, including the EGFR and NFB signaling pathways (71). Hyaluronan triggers the CD44-EGFR signaling pathway, which up-regulates hyaluronan synthesis in a positive feedback mechanism (33)(34)(35)(36)(37). Moreover, hyaluronan synthases have NFB binding regions in their promoters and are up-regulated by NFB agonists, such as IL-1␤ and TNF␣ (25, 38 -40).…”

Section: V3 Resists Monocyte Adhesion By Altering Signaling Pathwaysmentioning

confidence: 99%

Expression of Versican V3 by Arterial Smooth Muscle Cells Alters Tumor Growth Factor β (TGFβ)-, Epidermal Growth Factor (EGF)-, and Nuclear Factor κB (NFκB)-dependent Signaling Pathways, Creating a Microenvironment That Resists Monocyte Adhesion

Kang

Yoon

Braun

et al. 2014

Journal of Biological Chemistry

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Background: Monocyte accumulation contributes to inflammatory disease progression. Results: ASMCs overexpressing V3 resist monocyte adhesion by promoting elastogenesis, depleting hyaluronan, and reducing VCAM1, via differentially regulating TGF␤-, EGF-, and NFB-signaling pathways. Conclusion: V3 expression by ASMCs generates a microenvironment resistant to monocyte adhesion. Significance: Modifying ECM components via V3 expression alters monocyte adhesion, which suggests therapeutic possibilities to treat inflammation.

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Heregulin-mediated ErbB2-ERK Signaling Activates Hyaluronan Synthases Leading to CD44-dependent Ovarian Tumor Cell Growth and Migration

Cited by 139 publications

References 87 publications

Hyaluronan-mediated CD44 activation of RhoGTPase signaling and cytoskeleton function promotes tumor progression

Hyaluronan-mediated CD44 activation of RhoGTPase signaling and cytoskeleton function promotes tumor progression

Potentially important microRNA cluster on chromosome 17p13.1 in primary peritoneal carcinoma

Expression of Versican V3 by Arterial Smooth Muscle Cells Alters Tumor Growth Factor β (TGFβ)-, Epidermal Growth Factor (EGF)-, and Nuclear Factor κB (NFκB)-dependent Signaling Pathways, Creating a Microenvironment That Resists Monocyte Adhesion

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