2009
DOI: 10.1074/jbc.m806772200
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Abstract: Our studies have shown that constitutive interactions between hyaluronan and CD44 on tumor cells induces various anti-apoptotic cell survival pathways through the formation of a multimeric signaling complex that contains activated receptor tyrosine kinases. Inhibition of the hyaluronan-CD44 interactions on tumor cells by hyaluronan-CD44 interaction antagonists suppresses these activities by disassembling the complex. Although the anti-tumor activity of hyaluronan-oligosaccharides, a hyaluronan-CD44 interaction… Show more

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Cited by 84 publications
(71 citation statements)
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References 70 publications
(61 reference statements)
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“…In Apc Min/+ mice that develop spontaneously colorectal carcinoma with high expression of CD44 variant isoforms, the tissue-specific delivery of siRNA was performed using a colon-specific promoter. The expression of CD44v6-specific shRNA led to the reduction of tumors in these mice (Misra et al 2009). This approach is highly flexible since the use of specific shRNA and tissue-specific promoters for expression of the Cre recombinase allow its application for several tumor types and target genes.…”
Section: Inhibition Of Cd44 Expressionmentioning
confidence: 95%
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“…In Apc Min/+ mice that develop spontaneously colorectal carcinoma with high expression of CD44 variant isoforms, the tissue-specific delivery of siRNA was performed using a colon-specific promoter. The expression of CD44v6-specific shRNA led to the reduction of tumors in these mice (Misra et al 2009). This approach is highly flexible since the use of specific shRNA and tissue-specific promoters for expression of the Cre recombinase allow its application for several tumor types and target genes.…”
Section: Inhibition Of Cd44 Expressionmentioning
confidence: 95%
“…Several mechanisms have been proposed that account for this function. Among these are the HA-dependent activation of TGFβ1 (Yu and Stamenkovic 2004), the activation of HB-EGF, the activation of osteopontin by CD44v6 containing isoforms and even the inhibition of Fas signaling by CD44 (reviewed in Ponta et al 2003;Mielgo et al 2005). A completely different function of CD44 in apoptosis was recently suggested.…”
Section: Cd44 Isoforms Act As Co-receptorsmentioning
confidence: 98%
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“…The celecoxib, licofelone, sulforaphane (SFN), phenyl isothiocyanate (PITSC), antibodies against CD44v6, COX-2, 5-LOX, caspase 3, β-actin, horse radish peroxidase-linked anti-rabbit and anti-mouse antibodies, and Luminol reagent were purchased from commercial sources (Sigma, Santa Cruz Biotechnology, Abcam, Ebioscience, Thermo Fischer). CD44v6shrNA or controlshRNA are designed as described in our earlier studies (Misra et al , 2009). …”
Section: Experimental Protocolsmentioning
confidence: 99%
“…Attempts are underway in identifying molecules that are specifically expressed by epithelial tumor cells which correlate with tumor growth and drug resistance. Among such molecules hyaluronic acid (HA), is a major extracellular matrix (ECM) component (Misra et al , 2009) whose interaction with the receptor variant isoform CD44v6 (Aruffo et al , 1990) has been suggested to play a crucial role in regulating COX-2/PGE2 mediated cell survival, motility, and drug resistance (Lesley et al , 2000a, b; Lesley and Hyman, 1992; Naor et al , 2002; Yamada et al , 2004). We had earlier demonstrated that the reversal of HA/CD44v6 signaling can modulate the cancer phenotype and adenoma growth in Apc Min/+ mice by inhibiting CD44v6/ErbB2/COX-2-PGE2 pathway (Ghatak et al , 2008, 2010), suggesting the potential of HA/CD44v6 as target for anti-cancer/chemopreventive drugs.…”
Section: Introductionmentioning
confidence: 99%