Interaction between the Adhesion Receptor, CD44, and the Oncogene Product, p185 , Promotes Human Ovarian Tumor Cell Activation

Abstract

In this study we have examined the interaction between CD44s (the standard form) and the p185 HER2 proto-oncogene in the ovarian carcinoma cell line. Surface biotinylation followed by wheat germ agglutinin column chromatography and anti-CD44-mediated immunoprecipitation indicate that both CD44s and p185 HER2 are expressed on the cell surface and most importantly, that these two molecules are physically linked to each other via interchain disulfide bonds. We have also determined that hyaluronic acid stimulates CD44s-associated p185 HER2 tyrosine kinase activity, leading to an increase in the ovarian carcinoma cell growth.After transfection of the ovarian carcinoma cell line with the adenovirus 5 E1A gene, which is known to repress p185 HER2 expression, we observed that both surface CD44s expression and CD44s-mediated cell adhesion to hyaluronic acid are significantly reduced in the transfectant cells compared with the control cells. These data suggest that down-regulation of p185 HER2 blocks CD44s expression and subsequent adhesion function. Our findings also indicate that the CD44s-p185 HER2 interaction is both functionally coupled and biosynthetically regulated. We believe that direct "cross-talk" between these two surface molecules (i.e. CD44s and the p185 HER2 ) may be one of the most important signaling events in human ovarian carcinoma development.

Hyaluronan is required for cranial neural crest cells migration and craniofacial development

“…These findings suggest that the formation of hyaluronan-versican complexes may help to facilitate cranial NCC migration. Hyaluronan can promote cell locomotion also by interacting with cell membrane receptors, which modulate cell adhesion and trigger intracellular signaling (Bourguignon et al, 1997;Banerji et al, 1999;Tzircotis et al, 2005). The finding that CD44 down-regulated embryos exhibit an NCC migration delayed phenotype, similar to that observed in embryos depleted of both Has1 and Has2, suggests that CD44 could mediate the hyaluronan instructive effect that initiates signaling pathways and thus promotes NCC movements.…”

Ankyrin–Tiam1 Interaction Promotes Rac1 Signaling and Metastatic Breast Tumor Cell Invasion and Migration

“…Ankyrin is known to bind to a number of plasma membrane–associated proteins including the following: band 3, two other members of the anion exchange gene family (Bennet, 1992), Na + /K + -ATPase (Nelson and Veshnock 1987; Zhang et al 1998), the amiloride-sensitive Na + channel (Smith et al 1991), the voltage-dependent Na + channel (Kordeli et al 1995), Ca 2+ channels (Bourguignon et al 1993b, Bourguignon et al 1995a; Bourguignon and Jin 1995) and the adhesion molecule CD44 (Bourguignon et al 1986, Bourguignon et al 1991, Bourguignon et al 1992, Bourguignon et al 1993a; Kalomiris and Bourguignon 1988, Kalomiris and Bourguignon 1989; Lokeshwar and Bourguignon 1991, Lokeshwar and Bourguignon 1992; Lokeshwar et al 1994, Lokeshwar et al 1996). It has been suggested that the binding of ankyrin to certain membrane-associated molecules is necessary for signal transduction, cell adhesion, membrane transport, cell growth, migration, and tumor metastasis (Bennet, 1992; Bourguignon et al 1995b, 1996, Bourguignon et al 1997, Bourguignon et al 1998a; De Matteis and Morrow 1998; Zhu and Bourguignon 1998, Zhu and Bourguignon 2000). …”

The interaction of versican with its binding partners

“…Hyaluronan-CD44 signaling can activate several pathways through activation of specific intermediates [39]. These include, but are not limited to, the Rho and Rac1 GTPases, whose activities lead to subsequent reorganization of the actin cytoskeleton [40][41][42]; erbB2 tyrosine kinase [43], which leads to cell proliferation; src-related tyrosine kinases [44], and nuclear factor-κB [NF-κB] [45,46]. Hyaluronan and CD44 interaction have also been known to affect cell adhesion and migration.…”