Regulation of alternative splicing of CD44 in cancer

Procházka, Lubomír; Tesařı́k, Radek; Tuřánek, Jaroslav

doi:10.1016/j.cellsig.2014.07.011

Cited by 167 publications

(155 citation statements)

References 76 publications

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“…However, involvement of other variable exons remains to be elucidated, especially because the transcript levels of other CD44 variable exons were also increased by knocking down HNRNPLL in SW480 cells (see online supplementary figure S2A). The roles of CD44 variant isoforms other than CD44v6 in cancer invasion and metastasis have been documented for several types of cancer 8 41. Notably, Saya et al reported that a subpopulation of 4T1 breast cancer cells expressing CD44v8–10 showed high lung-metastatic ability in an orthotopic transplantation model, in a manner dependent on interaction between the cystine transporter cystine/glutamate transporter (xCT) and CD44v8–10 42 43…”

Section: Discussionmentioning

confidence: 99%

HNRNPLL, a newly identified colorectal cancer metastasis suppressor, modulates alternative splicing of CD44 during epithelial-mesenchymal transition

Sakuma

Sasaki

Kimura

et al. 2017

Gut

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Section: Discussionmentioning

confidence: 99%

HNRNPLL, a newly identified colorectal cancer metastasis suppressor, modulates alternative splicing of CD44 during epithelial-mesenchymal transition

Sakuma

Sasaki

Kimura

et al. 2017

Gut

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“…Splicing to CD44s enables interaction with hyaluronic acid, activating TGF-β signaling among other pathways [44, 45]. This isoform switching is a critical attribute of the tumor initiating cell subpopulation [46]. …”

Section: Resultsmentioning

confidence: 99%

Motility and stem cell properties induced by the epithelial-mesenchymal transition require destabilization of lipid rafts

et al. 2016

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The Epithelial-Mesenchymal Transition (EMT) is a developmental program that provides cancer cells with the characteristics necessary for metastasis, including increased motility and stem cell properties. The cellular and molecular mechanisms underlying this process are not yet fully understood, hampering efforts to develop therapeutics. In recent years, it has become apparent that EMT is accompanied by wholesale changes in diverse signaling pathways that are initiated by proteins at the plasma membrane (PM). The PM contains thousands of lipid and protein species that are dynamically and spatially organized into lateral membrane domains, an example of which are lipid rafts. Since one of the major functions of rafts is modulation of signaling originating at the PM, we hypothesized that the signaling changes occurring during an EMT are associated with alterations in PM organization. To test this hypothesis, we used Giant Plasma Membrane Vesicles (GPMVs) to study the organization of intact plasma membranes isolated from live cells. We observed that induction of EMT significantly destabilized lipid raft domains. Further, this reduction in stability was crucial for the maintenance of the stem cell phenotype and EMT-induced remodeling of PM-orchestrated pathways. Exogenously increasing raft stability by feeding cells with ω-3 polyunsaturated fatty acid docosahexaenoic acid (DHA) repressed these phenotypes without altering EMT markers, and inhibited the metastatic capacity of breast cancer cells. Hence, modulating raft properties regulates cell phenotype, suggesting a novel approach for targeting the impact of EMT in cancer.

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“…Transcripts for the CD44 gene undergo complicated alternative splicing, which results in many functionally distinct protein isoforms, such as CD44 standard (CD44s) and CD44 variant isoforms (CD44v), which account for the heterogeneity in this protein family145. It is widely accepted that CD44 is expressed as multiple transcriptional variants, but the 3′UTR, which is ~3000 nucleotides long, is in fact relatively conserved214.…”

Section: Discussionmentioning

confidence: 99%

“…First, CD44 is found to be widely expressed in various cancers, and its expression correlates with poor prognosis1345. In functional studies, specific targeted knockdown of CD44 has been shown to impede cancer progression6.…”

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confidence: 99%

Associations of five polymorphisms in the CD44 gene with cancer susceptibility in Asians

Wang

Chen

et al. 2016

Sci Rep

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CD44 polymorphisms have been previously associated with cancer risk. However, the results between independent studies were inconsistent. Here, a meta-analysis was performed to systematically evaluate associations between CD44 polymorphisms and cancer susceptibility. A comprehensive literature search conducted in PubMed, Embase, and Web of Science databases through August 10, 2016 yielded 11 eligible publications consisting of 5,788 cancer patients and 5,852 controls. Overall, odds ratios (OR) calculated with 95% confidence intervals (CI) identified a significant association between CD44 polymorphism rs13347 and cancer susceptibility under all genetic models. Additionally, the minor allele of polymorphism rs11821102 was associated with a decreased susceptibility to cancer in allele contrast, dominant, and heterozygous models, while no significant association was identified for polymorphisms rs10836347, rs713330, or rs1425802. Subgroup analysis by ethnicity revealed rs13347 was significantly associated with cancer susceptibility for Chinese but not for Indians. Linkage disequilibrium (LD) between different polymorphisms varied across diverse ethnic populations. In conclusion, the results indicate that CD44 polymorphism rs13347 acts as a risk factor for cancer, especially in Chinese, while the minor allele of polymorphism rs11821102 may be associated with a decreased susceptibility to cancer. Nevertheless, further studies on a larger population covering different ethnicities are warranted.

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Regulation of alternative splicing of CD44 in cancer

Cited by 167 publications

References 76 publications

HNRNPLL, a newly identified colorectal cancer metastasis suppressor, modulates alternative splicing of CD44 during epithelial-mesenchymal transition

HNRNPLL, a newly identified colorectal cancer metastasis suppressor, modulates alternative splicing of CD44 during epithelial-mesenchymal transition

Motility and stem cell properties induced by the epithelial-mesenchymal transition require destabilization of lipid rafts

Associations of five polymorphisms in the CD44 gene with cancer susceptibility in Asians

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