Induction of carcinoma cell migration on vitronectin by NF-kappa B-dependent gene expression.

Abstract

Integrin avf35 promotes FG carcinoma cell adhesion to vitronectin yet requires protein kinase C (PKC) activation for migration on this ligand. Here we report that this PKCdependent cell motility event requires NF-KB-dependent transcription. Specifically, a component within nuclear extracts prepared from PKC-stimulated FG cells exhibited a significant increase in binding activity to a synthetic oligonucleotide containing a consensus KB sequence. These nuclear DNA-binding complexes were shown to be comprised of p65 and p50 NF-KB/rel family members and appeared functionally active because they promoted transcription of a reporter construct containing a KB site. The NF-KB activation event was directly linked to the av,35 motility response because the NF-KB-binding oligonucleotide, when introduced into FG cells, inhibited cell migration on vitronectin but not on collagen and had no effect on cell adhesion to either ligand. These results suggest that the detected DNA-binding complexes interact with KB transcriptional elements to regulate gene expression required for avp35-dependent cell motility on vitronectin. INTRODUCTION Regulation of cell migration is a critical factor during tissue remodeling associated with angiogenesis, embryogenesis, inflammation, and wound healing (Albelda and Buck, 1990). Upon neoplastic transformation, cells acquire a migratory phenotype that facilitates their ability to metastasize. Integrins are cell surface receptors that mediate cell-matrix interactions critical for cell motility (Ruoslahti, 1991;Hynes, 1992;Leavesley et al., 1992Leavesley et al., , 1993Klemke et al., 1994). Although integrin-mediated cell adhesion is necessary for migration, it is not always sufficient. For example, recent studies have shown that integrin-dependent cell motility, but not attachment, requires the presence of exogenous growth factors Matthay et al., 1993;Klemke et al., 1994), suggesting that cell motility involves activation events not required for adhesion.t Corresponding author.FG pancreatic carcinoma cells attach to vitronectin utilizing integrin av,85, yet are unable to migrate on this ligand even though they attach and migrate on collagen in an a2f31 integrin-dependent manner (Leavesley et al., 1992). These findings indicate that FG cell migration on collagen is constitutive whereas av135-dependent migration on vitronectin requires agonist activation. However, we recently showed that FG cells can be induced to migrate on vitronectin in the presence of soluble growth factors, such as epidermal growth factor and insulin-like growth factor, which act by stimulating a PKC-dependent signaling pathway (Klemke et al., 1994).PKC is known to activate the adhesive properties of some cells by enhancing the affinity of their cell surface integrins (Shattil and Brass, 1987;Hibbs et al., 1991;Valmu et al., 1991;Wilkins et al., 1991; MartinThouvenin et al., 1992). In addition, PKC potentiates signaling events leading to integrin-dependent cell spreading and motility (Vuori and Ruoslahti, 1993;Klemke et al., 1994...

Melanoma cell migration to type IV collagen requires activation of NF-κB

“…Although other groups have suggested that NF-kB is involved in the migration of pancreatic carcinoma or keratinocytes (Yebra et al, 1995;Benoliel et al, 1997), these previous studies provide little insight into events responsible for NF-kB induction. More importantly, our data indicated a significant increase in transcription of b1 integrin mRNA following the CIV treatment.…”

“…Recently, NF-kB has been shown to be required for cell migration mediated by some ECM proteins. For example, NF-kB was necessary for the migration of a pancreatic cell line in response to vitronectin, as well as the chemotaxis of keratinocytes in response to insulin (Yebra et al, 1995;Benoliel et al, 1997). Whether b1 integrindependent tumor cell migration requires the induction of transcription factors, including NF-kB, needs further elucidation.…”

An invasion-related complex of cortactin, paxillin and PKCμ associates with invadopodia at sites of extracellular matrix degradation

“…PKC activity is involved in integrin-mediated responses including adhesion, motility and membrane ru ing (Lewis et al, 1996;Klemke et al, 1994;Yebra et al, 1995;Miyata et al, 1989). It can also a ect invasive behavior (Ways et al, 1995).…”

Requirement of Receptor-bound Urokinase-type Plasminogen Activator for Integrin αvβ5-directed Cell Migration

“…The integrin family of cell adhesion receptors mediates cell attachment to extracellular matrix proteins and is known to play a critical role in cell motility (12)(13)(14)(15), thus contributing to a variety of biological processes including angiogenesis, wound healing, and tumor cell invasion and metastasis (16 -18).…”