Molecular and cellular basis of cancer invasion and metastasis: Implications for treatment

Jiang, Wen Guo; Puntis, M. C. A.; Hallett, Maurice Bartlett

doi:10.1002/bjs.1800811107

Cited by 121 publications

(56 citation statements)

References 171 publications

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“…It is now certain that both oncogenic signaling and cytoskeleton functions are directly involved in tumor cell growth, migration, invasion of surrounding tissue, and metastasis [4,5]. A number of studies have aimed at identifying these molecules which are specifically expressed by epithelial tumor cells which correlate with metastatic behavior.…”

Section: Hyaluronan (Ha) and Cd44 In Tumor Progressionmentioning

confidence: 99%

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

Bourguignon

2008

Seminars in Cancer Biology

271

279

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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: Hyaluronan (Ha) and Cd44 In Tumor Progressionmentioning

confidence: 99%

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

Bourguignon

2008

Seminars in Cancer Biology

271

279

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“…Signaling and Cytoskeleton-mediated Tumor Cell Migration-Previous studies indicate that the invasive phenotype of tumor cells characterized by an invadopodia structure (or membranous projections) (56,57) and tumor cell migration (28,29) is closely associated with CD44v 3,8 -10 -linked cytoskeleton function (23). In this study we have transiently transfected breast tumor cells (e.g.…”

Section: Cd44v3-tiam1 Interaction In Rac1mentioning

confidence: 99%

“…For example, activation of RhoA, Rac1, and Cdc42 have been shown to produce specific structural changes in the plasma membrane-cytoskeleton reorganization leading to membrane ruffling, lamellipodia, filopodia, and stress fiber formation (26). The coordinated activation of these GTPases is considered to be a possible mechanism underlying cell motility, an obvious prerequisite for metastasis (27)(28)(29). In particular, Rac1 activation is known to initiate oncogenic signaling pathways that promote cell shape changes (33,34), influence actin cytoskeleton organization (33,34), and stimulate gene expression (35)(36)(37).…”

Section: From the Department Of Cell Biology And Anatomy School Of Mmentioning

confidence: 99%

CD44 Interaction with Tiam1 Promotes Rac1 Signaling and Hyaluronic Acid-mediated Breast Tumor Cell Migration

Bourguignon¹,

Zhu

Shao

et al. 2000

Journal of Biological Chemistry

267

237

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In this study we have explored the interaction between CD44 (the hyaluronic acid ( The transmembrane glycoprotein CD44 isoforms are all major hyaluronic acid (HA) 1 cell surface receptors that exist on many cell types, including macrophages, lymphocytes, fibroblasts, and epithelial cells (1-6). Because of their widespread occurrence and their role in signal transduction, CD44 isoforms have been implicated in the regulation of cell growth and activation as well as cell-cell and cell-extracellular matrix interactions (1-7). One of the distinct features of CD44 isoforms is the enormous heterogeneity in the molecular masses of these proteins. It is now known that all CD44 isoforms are encoded by a single gene that contains 19 exons (8). Of the 19 exons, 12 exons can be alternatively spliced (8). Most often, the alternative splicing occurs between exons 5 and 15, leading to an insertion in tandem of one or more variant exons (v1-v10 (exon 6-exon 14) in human cells) within the membrane-proximal region of the extracellular domain (8). The variable primary amino acid sequence of different CD44 isoforms is further modified by extensive N-and O-glycosylations and glycosaminoglycan additions (9 -12). In particular, CD44v3-containing isoforms have a heparin sulfate addition at the membrane-proximal extracellular domain of the molecule that confers the ability to bind heparin sulfate-binding growth factors (9, 10). Cell surface expression of CD44v isoforms changes profoundly during tumor metastasis, particularly during the progression of various carcinomas including breast carcinomas (13-17). In fact, CD44v isoform expression has been used as an indicator of metastasis.It has been shown that interaction between the cytoskeletal protein, ankyrin, and the cytoplasmic domain of CD44 isoforms plays an important role in CD44 isoform-mediated oncogenic signaling (6,18,19). Specifically, the ankyrin-binding domain (e.g. NGGNGTVEDRKPSEL between amino acids 306 and 320 in the mouse CD44 (20) and NSGNGAVEDRKPSGL amino acids 304 and 318 in human CD44 (21)) is required for the recruitment of Src kinase and the onset of tumor cell transformation (21). Furthermore, HA binding to CD44 stimulates a concomitant activation of p185 HER2 -linked tyrosine kinase (linked to CD44s via a disulfide linkage) and results in a direct cross-talk between two different signaling pathways (e.g. proliferation versus motility/invasion) (22). In tumor cells, the transmembrane linkage between CD44 isoform and the cytoskeleton promotes invasive and metastatic-specific tumor phenotypes (e.g. matrix degradation (matrix metalloproteinases) activities (23, 24), "invadopodia" formation (membrane projections), tumor cell invasion, and migration) (23). These findings strongly suggest that the interaction between CD44 isoform and the cytoskeleton plays a pivotal role in the onset of oncogenesis and tumor progression.The Rho family proteins (e.g. Rho, Rac, and Cdc42) are members of the Ras superfamily of GTP-binding proteins structurally related to but functionally dist...

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“…For example, activation of Rac1, RhoA, and Cdc42 has been shown to produce specific structural changes in the plasma membrane cytoskeleton associated with membrane ruffling, lamellipodia, filopodia, and stress fiber formation (Ridley and Hall 1992; Hall 1998). The coordinated activation of these GTPases is thought to be a possible mechanism underlying cell motility, an obvious prerequisite for metastasis (Jiang et al 1994; Dickson and Lippman 1995; Lauffenburger and Horwitz 1996). …”

Section: Introductionmentioning

confidence: 99%

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

Bourguignon

Zhu

Shao

et al. 2000

The Journal of Cell Biology

116

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Tiam1 (T-lymphoma invasion and metastasis 1) is one of the known guanine nucleotide (GDP/GTP) exchange factors (GEFs) for Rho GTPases (e.g., Rac1) and is expressed in breast tumor cells (e.g., SP-1 cell line). Immunoprecipitation and immunoblot analyses indicate that Tiam1 and the cytoskeletal protein, ankyrin, are physically associated as a complex in vivo. In particular, the ankyrin repeat domain (ARD) of ankyrin is responsible for Tiam1 binding. Biochemical studies and deletion mutation analyses indicate that the 11–amino acid sequence between amino acids 717 and 727 of Tiam1 (717GEGTDAVKRS727L) is the ankyrin-binding domain. Most importantly, ankyrin binding to Tiam1 activates GDP/GTP exchange on Rho GTPases (e.g., Rac1).Using an Escherichia coli–derived calmodulin-binding peptide (CBP)–tagged recombinant Tiam1 (amino acids 393–728) fragment that contains the ankyrin-binding domain, we have detected a specific binding interaction between the Tiam1 (amino acids 393–738) fragment and ankyrin in vitro. This Tiam1 fragment also acts as a potent competitive inhibitor for Tiam1 binding to ankyrin. Transfection of SP-1 cell with Tiam1 cDNAs stimulates all of the following: (1) Tiam1–ankyrin association in the membrane projection; (2) Rac1 activation; and (3) breast tumor cell invasion and migration. Cotransfection of SP1 cells with green fluorescent protein (GFP)–tagged Tiam1 fragment cDNA and Tiam1 cDNA effectively blocks Tiam1–ankyrin colocalization in the cell membrane, and inhibits GDP/GTP exchange on Rac1 by ankyrin-associated Tiam1 and tumor-specific phenotypes. These findings suggest that ankyrin–Tiam1 interaction plays a pivotal role in regulating Rac1 signaling and cytoskeleton function required for oncogenic signaling and metastatic breast tumor cell progression.

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Molecular and cellular basis of cancer invasion and metastasis: Implications for treatment

Cited by 121 publications

References 171 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

CD44 Interaction with Tiam1 Promotes Rac1 Signaling and Hyaluronic Acid-mediated Breast Tumor Cell Migration

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

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