CD43 has a functional NLS, interacts with β-catenin, and affects gene expression

Andersson, Christian X.; Fernández-Rodrı́guez, Julia; Laos, Sirle; Sikut, Rein; Sikut, Anu; Baeckström, Dan; Hansson, Gunnar C.

doi:10.1016/j.bbrc.2004.02.011

Cited by 34 publications

(57 citation statements)

References 21 publications

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“…Upon addition of the proteasome inhibitor none of these CD43 fragments translocate to the chromatin-bound nuclear fraction, the fragments appeared only in the fractions where CD43-CTF accumulated. This is somewhat contradictory to the published data indicating that CD43ct binds β-catenin to activate the expression of β-catenin target genes MYC and cyclin D1 (24). However, the presence of the mature CD43 in the chromatinbound nuclear fraction and the failure of the CD43 cytoplasmic fragments to accumulate in this fraction correlate with our results showing that the overexpression of the full-length CD43, and not the CD43ct, helps the cells with defective ARF-p53 signaling to evade Fas-mediated apoptosis and promotes cell growth (35).…”

Section: Discussioncontrasting

confidence: 96%

“…Moreover, we found that cells overexpressing CD43 are more resistant to Fas-mediated apoptosis, the mechanism possibly giving these cells the growth advantage (35). In addition, CD43 has been suggested to have a role in Wnt/β-catenin signaling as the cytoplasmic tail of CD43 interacts with β-catenin and promotes its target gene expression (24).…”

Section: Introductionmentioning

confidence: 84%

“…When either ARF or p53 is absent, CD43 overexpressing cells gain growth advantage due to the better survival of these cells. In addition, cytoplasmic tail of CD43 has been shown to interact with β-catenin and induce expression of its target genes (24). This suggests that CD43 is involved in colon tumor development via Wnt signaling pathway.…”

Section: Discussionmentioning

confidence: 99%

“…While in blood cells CD43 is expressed on the cell membrane, in nonhematopoietic cancer cells, in contrast, CD43 is located primarily intracellularly and even nuclearly (23). The cytoplasmic domain of CD43 contains a functional NLS (nuclear localization signal) and interacts with the nuclear transporter protein Ran which offers an explanation for the nuclear localization of CD43 (24). The translocation of the cytoplasmic part of CD43 to the nucleus is possible due to its γ-secretase-dependent proteolytic removal from the membrane.…”

Section: Introductionmentioning

confidence: 99%

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Leukocyte marker CD43 promotes cell growth in co-operation with β-catenin in non-hematopoietic cancer cells

et al. 2012

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Abstract. The Wnt/β-catenin pathway regulates key cellular processes such as differentiation, proliferation, apoptosis; and its activation promotes development of several cancer types. Expression of CD43 (leukosialin), the predominant leukocyte transmembrane sialoglycoprotein, has been detected in many tumors of non-hematopoietic origin. CD43 participates in cell adhesion and regulates intracellular signal transduction pathways involved in cell proliferation and survival. The cytoplasmic domain of CD43 has been reported to translocate to the nucleus, interact with β-catenin and affect its target gene expression, but the impact of this action on cell fate is still unknown. We demonstrate, here, by colony formation assay and siRNA-mediated gene silencing that CD43 and β-catenin co-operate in promoting cell growth. Moreover, in cells with down-regulated β-catenin expression the activation of p53 in response to CD43 overexpression is significantly impaired. In addition, the presence of both CD43 and β-catenin is required for the TCF/LEF-mediated transcription. Presumably, the fulllength CD43 participates in this transcriptional regulation. We show that the mature CD43 localizes to the nucleus, where it binds chromatin, co-localizes and co-immunoprecipitates with β-catenin, and enhances the reporter gene expression regulated by β-catenin. These observations provide clear evidence linking CD43 to the Wnt/APC/β-catenin signaling pathway and supporting our hypothesis according to which CD43 plays a role in tumor development.

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Section: Discussioncontrasting

confidence: 96%

Section: Introductionmentioning

confidence: 84%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Leukocyte marker CD43 promotes cell growth in co-operation with β-catenin in non-hematopoietic cancer cells

et al. 2012

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“…However, it is tempting to speculate that nuclear localization of CD43 in lung cancer protects against apoptosis and changes gene expression as it does in leukocytes. 7,8 Cytoplasmic localization may not drive such processes and, therefore, may help to explain the generally less aggressive nature of colon compared to lung cancer. 1 A role for CD43 in driving the pathogenesis of lung cancer is suggested by extrapolating its anti-adhesion function in resting leukocytes and its pro-adhesion, migration and survival functions in activated leukocytes.…”

Section: Discussionmentioning

confidence: 99%

CD43 in the nucleus and cytoplasm of lung cancer is a potential therapeutic target

Cash

Andersen

et al. 2012

Intl Journal of Cancer

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CD43 is a transmembrane sialoglycoprotein. Normally the molecule is only produced by white blood cells where it regulates functions such as intercellular adhesion, intracellular signaling, apoptosis, migration and proliferation. Two CD43 antibodies were used to interrogate 66 cases of non-small cell lung cancer (NSCLC) and 24 cases of small cell lung cancer (SCLC). In addition, we engineered the CD43-positive lung cancer cell line A549 to stably express either non-targeted or CD43-targeted small-interfering RNA (siRNA). These lines were then subjected to in vitro assays of apoptosis, natural killer (NK) cell cytotoxicity, intercellular adhesion and transendothelial migration. A xenograft mouse model evaluated the ability of the lines to grow primary tumors in vivo. CD43 was found to be expressed in the majority of both SCLC and NSCLC. Inclusive of CD43-negative tumors, differential patterns of nuclear and cytoplasmic expression of CD43 define four molecular subcategories of lung cancer. Targeting CD43 in A549 lung cancer cells, increased homotypic adhesion, decreased heterotypic adhesion and transendothelial migration, increased susceptibility to apoptosis and increased vulnerability to lysis by NK cells. Furthermore, targeting inhibited the growth of primary tumors in nude mice.Despite major advances in the field of medical oncology, lung cancer remains the leading cause of cancer death in the United States among both men and women. With an estimated 221,130 new cases and 156,940 deaths in 2011, lung cancer is responsible for more than 25% of all cancer deaths. 1 Two studies have reported that lung cancer might be characterized by expression of the sialoglycoprotein CD43 normally only produced by leukocytes. 2,3 The first study reported that 13 out of 13 cases of non-small cell lung cancer (NSCLC) expressed CD43 while two out of two cases of small cell lung cancer (SCLC) were CD43-negative. 2 The second study reported that one out of three primary lung tumors exhibited CD43 expression. 3 One of these three tumors was a smallcell carcinoma and the other two were squamous cell carcinomas. Here, we report the analysis of 90 cases of lung cancer using antibodies that recognize either the N or C terminus of CD43. In addition, we report the functional consequences of expressing CD43-targeted small-interfering RNA (siRNA) in the lung cancer cell line A549. Material and Methods Patient materialParaffin-embedded formalin-fixed tissues representing 90 cases of lung cancer and one mild case of lung silicosis were provided free-of-charge by the Gundersen Foundation BioBank (http://www.gundluth.org/biobank). Each case was sectioned, stained with hematoxylin and eosin and the histological diagnosis verified. All experimental procedures were

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CD43 – One molecule, many tales to recount

Pedraza‐Alva

Rosenstein²

2007

Signal Transduction

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Immune cells functions are regulated through the orchestrated intervention of immune receptors that recognize non-self peptides or pathogen associated molecular patterns and of molecules that modulate the signals these receptors generate. These molecules, known as accessory or co-receptor molecules, sense the environment, setting the threshold for cell activation, as well as instructing the cells to ensure self-tolerance and homeostasis. CD43 is an abundant cell surface protein, expressed on nearly all lineages of hematopoietic cells. Multiple, and sometimes opposite functions, have been attributed to CD43: adhesion and anti-adhesion, locomotion, cellular activation, differentiation, proliferation and apoptosis. Here we will summarize recent developments in our understanding of the role this molecule plays in different cell types. In particular, we will illustrate the role of CD43 as a T cell accessory molecule, capable of generating intracellular signals, independently of or in coordination with the TCR, actively modulating T cell response. In addition, we review new functions for this molecule, in non-immune cells.

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CD43 has a functional NLS, interacts with β-catenin, and affects gene expression

Cited by 34 publications

References 21 publications

Leukocyte marker CD43 promotes cell growth in co-operation with β-catenin in non-hematopoietic cancer cells

Leukocyte marker CD43 promotes cell growth in co-operation with β-catenin in non-hematopoietic cancer cells

CD43 in the nucleus and cytoplasm of lung cancer is a potential therapeutic target

CD43 – One molecule, many tales to recount

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