CD44v3 levels in primary cutaneous melanoma are predictive of prognosis: Assessment by the use of tissue microarray

Pacifico, Marc D.; Grover, Rajiv; Richman, P. I.; Daley, Frances; Buffa, Francesca M.; Wilson, George D.

doi:10.1002/ijc.21504

Cited by 23 publications

(16 citation statements)

References 31 publications

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“…Furthermore, CD44v3 expression showed a negative correlation with local recurrence, secondary metastasis to lymph nodes, and survival rate. Mark et al reported that decreased CD44v3 expression in cutaneous melanoma correlated with poor outcome (31), which supports the results of this study. On the other hand, we found that CD44v6 expression showed no correlation with clinicopathological parameters in patients with OSCCT.…”

Section: Discussionsupporting

confidence: 92%

“…The functions of these isoforms remain relatively unclear (32). However, CD44 molecules containing the v3 domain is the only CD44 isoform able to bind heparin-binding growth factors and cytokines through its heparin sulfate side chains (31,33). For example, Grimme et al reported that CD44v3 is modified with heparin sulfate (HS) and binds HS-binding basic fibroblast growth factor (bFGF), and they suggested that HS-binding bFGF presented by the HS-modified CD44v3 may stimulate the proliferation of normal or malignantly transformed keratinocytes in skin (34).…”

Section: Discussionmentioning

confidence: 99%

“…For example, Grimme et al reported that CD44v3 is modified with heparin sulfate (HS) and binds HS-binding basic fibroblast growth factor (bFGF), and they suggested that HS-binding bFGF presented by the HS-modified CD44v3 may stimulate the proliferation of normal or malignantly transformed keratinocytes in skin (34). It is hypothesized that tumor cells expressing CD44v3 may therefore accumulate matrix-bound growth factors and play a role in the control of cellular proliferation (31). This could improve the survival of tumor cells remaining in their original environment and relieve the selective pressure to progress toward a metastasis-forming phenotype (28,31,33).…”

Section: Discussionmentioning

confidence: 99%

“…It is hypothesized that tumor cells expressing CD44v3 may therefore accumulate matrix-bound growth factors and play a role in the control of cellular proliferation (31). This could improve the survival of tumor cells remaining in their original environment and relieve the selective pressure to progress toward a metastasis-forming phenotype (28,31,33). Therefore, the loss of CD44 CD44v3 expression in tumor cells might be associated with increased metastatic potential and poor prognosis.…”

Section: Discussionmentioning

confidence: 99%

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Prognostic significance of CD44v3 and CD44v6 in oral squamous cell carcinoma of the tongue

et al. 2011

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Background: CD44, a family of alternatively spliced transmembrane cell adhesion molecules, is expressed in many types of tumors, including oral squamous cell carcinoma. CD44 variant 3 and 6 (CD44v3 and CD44v6) expression in head and neck squamous cell carcinoma has been suggested to correlate with a poor prognosis. We investigated the relationship between CD44 variant forms and clinicopathological parameters in oral squamous cell carcinoma of the tongue (OSCCT

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Prognostic significance of CD44v3 and CD44v6 in oral squamous cell carcinoma of the tongue

et al. 2011

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“…37 However, in melanoma and other cancer types CD44s was involved in tumor suppression. 23,44,45 Although several variant isoforms are blocking an invasive phenotype, [46][47][48] an opposing role of specific CD44v isoforms have been found to support tumor growth and malignancies (reviewed in Ref. 23).…”

Section: Discussionmentioning

confidence: 99%

A self‐enforcing CD44s/ZEB1 feedback loop maintains EMT and stemness properties in cancer cells

Preca

Bajdak

Mock

et al. 2015

Intl Journal of Cancer

160

138

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Invasion and metastasis of carcinomas are often activated by induction of aberrant epithelial-mesenchymal transition (EMT). This is mainly driven by the transcription factor ZEB1, promoting tumor-initiating capacity correlated with increased expression of the putative stem cell marker CD44. However, the direct link between ZEB1, CD44 and tumourigenesis is still enigmatic. Remarkably, EMT-induced repression of ESRP1 controls alternative splicing of CD44, causing a shift in the expression from the variant CD44v to the standard CD44s isoform. We analyzed whether CD44 and ZEB1 regulate each other and show that ZEB1 controls CD44s splicing by repression of ESRP1 in breast and pancreatic cancer. Intriguingly, CD44s itself activates the expression of ZEB1, resulting in a self-sustaining ZEB1 and CD44s expression. Activation of this novel CD44s-ZEB1 regulatory loop has functional impact on tumor cells, as evident by increased tumor-sphere initiation capacity, drug-resistance and tumor recurrence. In summary, we identified a self-enforcing feedback loop that employs CD44s to activate ZEB1 expression. This renders tumor cell stemness independent of external stimuli, as ZEB1 downregulates ESRP1, further promoting CD44s isoform synthesis.Tumor recurrence and metastasis represent the two major obstacles in the successful treatment of cancer. Increasing evidence suggests that the aggressive phenotype of this disease is associated with the activation of an embryonic program termed epithelial-mesenchymal transition (EMT), a process in which epithelial cells lose apical-basal cell polarity and change to a mesenchymal phenotype. [1][2][3] In order to initiate and complete an EMT, several distinct molecular programsKey words: cancer stem cells, epithelial-mesenchymal transition (EMT), metastasis, drug resistance, differential splicing Abbreviations: bHLH: basic helix-loop-helix; CD44s: cluster of differentiation 44, standard isoform; CD44v: cluster of differentiation 44, variant isoforms; ChIP: chromatin immunoprecipitation; CSC: cancer stem cell; Dox: doxycycline; EGF: epidermal growth factor; EMT: epithelial-mesenchymal transition; ESRP1: epithelial splicing regulatory protein 1; FGF: fibroblast growth factor; HGF/SF: hepatic growth factor/scatter factor; hnRNPM: heterogeneous nuclear ribonucleoprotein M; PDAC: pancreas ductal adenocarcinoma; shRNA: small hairpin ribonucleic acid; siRNA: small interference ribonucleic acid; TGFb: transforming growth factor b; ZEB: zinc-finger and E-box binding; ZFH: zinc-finger homeodomain

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The Sponge as a Model of Cellular Recognition

Fernàndez‐Busquets

Sourcebook of Models for Biomedical Research

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CD44v3 levels in primary cutaneous melanoma are predictive of prognosis: Assessment by the use of tissue microarray

Cited by 23 publications

References 31 publications

Prognostic significance of CD44v3 and CD44v6 in oral squamous cell carcinoma of the tongue

Prognostic significance of CD44v3 and CD44v6 in oral squamous cell carcinoma of the tongue

A self‐enforcing CD44s/ZEB1 feedback loop maintains EMT and stemness properties in cancer cells

The Sponge as a Model of Cellular Recognition

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