Estrogen receptor mediated inhibition of cancer cell invasion and motility: An overview

Rochefort, Henri; Platet, Nadine; Hayashido, Yasutaka; Derocq, Danielle; Lucas, Annick; Cunat, Séverine; Garcia, Marcel

doi:10.1016/s0960-0760(98)00010-7

Cited by 89 publications

(55 citation statements)

References 31 publications

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“…confirmed that the MDA-MB-231 and Ras-MCF10A aggressive breast cancer cell lines are more motile than either MCF7 or MCF10A cells as reported previously (63,73) (Fig. 6A).…”

Section: Cd44 and Cell Surface Rhamm Are Necessary For Motility Of Insupporting

confidence: 90%

The Hyaluronan Receptors CD44 and Rhamm (CD168) Form Complexes with ERK1,2 That Sustain High Basal Motility in Breast Cancer Cells

Hamilton

Fard

Paiwand

et al. 2007

Journal of Biological Chemistry

242

227

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CD44 is an integral hyaluronan receptor that can promote or inhibit motogenic signaling in tumor cells. Rhamm is a nonintegral cell surface hyaluronan receptor (CD168) and intracellular protein that promotes cell motility in culture. Here we describe an autocrine mechanism utilizing cell surface Rhamm-CD44 interactions to sustain rapid basal motility in invasive breast cancer cell lines that requires endogenous hyaluronan synthesis and the formation of Rhamm-CD44-ERK1,2 complexes. Motile/invasive MDA-MB-231 and Ras-MCF10A cells produce more endogenous hyaluronan, cell surface CD44 and Rhamm, an oncogenic Rhamm isoform, and exhibit more elevated basal activation of ERK1,2 than less invasive MCF7 and MCF10A breast cancer cells. Furthermore, CD44, Rhamm, and ERK1,2 uniquely co-immunoprecipitate and co-localize in MDA-MB-231 and Ras-MCF10A cells. Combinations of anti-CD44, anti-Rhamm antibodies, and a MEK1 inhibitor (PD098059) had less-than-additive blocking effects, suggesting the action of all three proteins on a common motogenic signaling pathway. Collectively, these results show that cell surface Rhamm and CD44 act together in a hyaluronan-dependent autocrine mechanism to coordinate sustained signaling through ERK1,2, leading to high basal motility of invasive breast cancer cells. Therefore, an effect of CD44 on tumor cell motility may depend in part on its ability to partner with additional proteins, such as cell surface Rhamm.Breast cancer invasion and progression involves a motile cell phenotype, which is under complex regulation by growth factors/cytokines and extracellular matrix (ECM) 4 components within the tumor microenvironment (1, 2). Motogenic signaling in tumor cells can be stimulated by both paracrine and autocrine factors; the latter decrease the requirement of invasive carcinomas for stromal support and are often associated with tumor progression (3-6). Hyaluronan (HA) (an anionic polymer of repeating units of glucuronic acid and N-acetylglucosamine) is one stromal ECM component that is associated with breast cancer progression (7,8). In culture, HA stimulates breast cancer cell motility (9 -11), pointing to a possible important role of this glycosaminoglycan in breast cancer cell invasion in vivo.

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“…confirmed that the MDA-MB-231 and Ras-MCF10A aggressive breast cancer cell lines are more motile than either MCF7 or MCF10A cells as reported previously (63,73) (Fig. 6A).…”

Section: Cd44 and Cell Surface Rhamm Are Necessary For Motility Of Insupporting

confidence: 90%

The Hyaluronan Receptors CD44 and Rhamm (CD168) Form Complexes with ERK1,2 That Sustain High Basal Motility in Breast Cancer Cells

Hamilton

Fard

Paiwand

et al. 2007

Journal of Biological Chemistry

242

227

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“…More recent studies have demonstrated that estradiol significantly reduces invasiveness and that this inhibition is reversed by antiestrogens [83][84][85][86][87]. This conclusion was noted in several ER-positive cancer cell lines established from breast [83] or ovary [85], and in different ER-negative cancer cells constitutively expressing ER after stable transfection [45,84,87]. Similar results were also obtained on the migration of normal cells from vascular smooth muscle [86].…”

Section: Estrogens Inhibit Invasion Via Ere-regulated Genessupporting

confidence: 66%

“…The initial studies indicated that the invasiveness of MCF7 breast cancer cells was increased by antiestrogens [81,82]. More recent studies have demonstrated that estradiol significantly reduces invasiveness and that this inhibition is reversed by antiestrogens [83][84][85][86][87]. This conclusion was noted in several ER-positive cancer cell lines established from breast [83] or ovary [85], and in different ER-negative cancer cells constitutively expressing ER after stable transfection [45,84,87].…”

Section: Estrogens Inhibit Invasion Via Ere-regulated Genesmentioning

confidence: 97%

Estrogens and their receptors in breast cancer progression: a dual role in cancer proliferation and invasion

Platet

Cathiard

Gleizes

et al. 2004

Critical Reviews in Oncology/Hematology

Self Cite

319

236

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Estrogens play an important role in regulating the growth and differentiation of normal, premalignant and malignant cell types, especially breast epithelial cells, through interaction with two nuclear estrogen receptors (ER and ERIn this review, we present a brief overview of the actions of estrogens in the different steps of breast carcinogenesis, including cancer progression to metastasis, and of their clinical consequences in the prevention, prognosis and treatment of the disease. The requirement of estrogen receptors, mainly of the alpha subtype, in normal mammary gland differentiation and growth has been evidenced by estrogen receptor deficiency in animals. The promotion of breast cancer carcinogenesis by prolonged exposure to estrogens is well-documented and this has logically led to the use of antiestrogens as potentially chemopreventive agents. In breast cancer progression, however, the exact roles of estrogen receptors have been less well established but they may possibly be dual. Estrogens are mitogenic in ER-positive cells and antiestrogens are an efficient adjuvant therapy for these tumors. On the other hand, the fact that estrogens and their receptors protect against cancer cell invasiveness through distinct mechanisms in experimental models may explain why the presence of ER is associated with well-differentiated and less invasive tumors.2

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“…Several previous studies have indicated an important role for E 2 in decreasing 'in vitro' invasiveness and motility of ERa-positive breast and ovarian cancer cells (Thompson et al, 1992;Hayashido et al, 1998;Rochefort et al, 1998). We found that cell adhesion on Fn and Col induces ERa translocation from the cytoplasm into the nucleus increasing the expression of estrogen-responsive genes, such as PS2 and cathepsin D, together with a downregulation of cell motility and invasion.…”

Section: Discussionsupporting

confidence: 48%

“…Many reports correlate ERa expression to lower matrigel invasiveness and to a reduced metastatic potential of breast cancer cell lines (Liotta et al, 1991;Thompson et al, 1992;Rochefort et al, 1998); however, the molecular mechanisms that define this process are still unclear. The interaction of cells with the extracellular matrix (ECM) influences many aspects of cell behavior, including growth, morphology, migratory properties and differentiation (Hynes, 1990;Clark and Brugge, 1995;Giancotti and Ruoslahti, 1999).…”

Section: Introductionmentioning

confidence: 99%

Fibronectin and type IV collagen activate ERα AF-1 by c-Src pathway: effect on breast cancer cell motility

et al. 2004

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The expression of estrogen receptor alpha (ERa) is generally associated with a less invasive and aggressive phenotype in breast carcinoma. In an attempt to understand the role of ERa in regulating breast cancer cells invasiveness, we have demonstrated that cell adhesion on fibronectin (Fn) and type IV Collagen (Col) induces ERamediated transcription and reduces cell migration in MCF-7 and in MDA-MB-231 cell lines expressing ERa. Analysis of deleted mutants of ERa indicates that the transcriptional activation function (AF)-1 is required for ERa-mediated transcription as well as for the inhibition of cell migration induced by cell adhesion on extracellular matrix (ECM) proteins. In addition, the nuclear localization signal region and some serine residues in the AF-1 of the ERa are both required for the regulation of cell invasiveness as we have observed in HeLa cells. It is worth noting that c-Src activation is coincident with adhesion of cells to ECM proteins and that the inhibition of c-Src activity by PP2 or the expression of a dominant-negative c-Src abolishes ERa-mediated transcription and partially reverts the inhibition of cell invasiveness in ERa-positive cancer cells. These findings address the integrated role of ECM proteins and ERa in influencing breast cancer cell motility through a mechanism that involves c-Src and seems not to be related to a specific cell type.

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Estrogen receptor mediated inhibition of cancer cell invasion and motility: An overview

Cited by 89 publications

References 31 publications

The Hyaluronan Receptors CD44 and Rhamm (CD168) Form Complexes with ERK1,2 That Sustain High Basal Motility in Breast Cancer Cells

The Hyaluronan Receptors CD44 and Rhamm (CD168) Form Complexes with ERK1,2 That Sustain High Basal Motility in Breast Cancer Cells

Estrogens and their receptors in breast cancer progression: a dual role in cancer proliferation and invasion

Fibronectin and type IV collagen activate ERα AF-1 by c-Src pathway: effect on breast cancer cell motility

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