Prognostic significance of nuclear or cytoplasmic nucleolin expression in human non-small cell lung cancer and its relationship with DNA-PKcs

Xu, Jian; Lü, Shan; Xu, Xin; Hu, Song; Li, Bin; Li, Wen xin; Chang, Joe Y.

doi:10.1007/s13277-016-4920-6

Cited by 34 publications

(42 citation statements)

References 19 publications

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“…There was notably higher expression of P-nucleolin in poorly-differentiated tumors compared with well-differentiated tumors. Nucleolin has been reported as an independent biomarker for poor prognosis in NSCLC (5,24) and the results of the present study provide additional evidence for this. More importantly, the authors' clinical data suggest that P-nucleolin may have the potential to be a more sensitive biomarker of cancer than nucleolin.…”

Section: Discussionsupporting

confidence: 78%

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Phosphorylation of nucleolin is indispensable to its involvement in the proliferation and migration of non-small cell lung cancer cells

Huang

Tan

et al. 2018

Oncol Rep

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Non-small cell lung cancer (NSCLC) is one of the mostly deadly malignancies in the world. Nucleolin is a multifunctional protein that mainly regulates ribosome biogenesis but also has other functions including modulating the transcription of mRNAs and repressing RNA polymerase II. Nucleolin is overexpressed in various cancer cells, including NSCLC cells. It can confer resistance to apoptosis and promote cell migration and blood vessel formation by directly taking part in various tumor signal transduction pathways. The activities of nucleolin are regulated mainly by intracellular localization and post-translational modifications, including phosphorylation, glycosylation, methylation, and ADP-ribosylation. Phosphorylation of nucleolin (P-nucleolin) in NSCLC cells is still not well characterized. In the present study, the levels of nucleolin and P-nucleolin were examined in lung tissue and cells and it was demonstrated that levels of the two forms of nucleolin were significantly increased in NSCLC compared with non-cancerous tissues and cells. In addition, it was demonstrated that high expression levels of nucleolin and P-nucleolin were significantly associated with poor overall survival of NSCLC patients. Doxorubicin (DOX) is a type of anthracycline that has been used in the treatment of various types of cancer, including NSCLC. Upregulation of nucleolin through exogenous expression of nucleolin promoted A549 cell proliferation and migration, while downregulation of nucleolin through expression of small interfering RNA-nucleolin attenuated A549 cell proliferation and migration. Following stimulation with DOX, A549 cell proliferation and migration decreased and the expression of P-nucleolin also decreased. In order to investigate whether P-nucleolin is indispensable to the proliferation and migration of NSCLC cells, a plasmid encoding mutant nucleolin, in which the phosphorylation site at threonine-76 was mutated to alanine, was constructed. Compared with the A549 cells transfected with wild-type nucleolin, P-nucleolin expression and cell proliferation and migration were significantly decreased in A549 cells transfected with mutant nucleolin. These results indicate that targeting P-nucleolin may be a promising strategy for treating NSCLC patients.

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Section: Discussionsupporting

confidence: 78%

“…Currently, various novel diagnostic and therapeutic targets for lung cancer are being studied (3,4). Recent evidence suggests that nucleolin, also known as C23, is a potent therapeutic target for the treatment of tumors (5)(6)(7). Nucleolin is a highly conserved multifunctional protein located in the nucleus.…”

Section: Introductionmentioning

confidence: 99%

Phosphorylation of nucleolin is indispensable to its involvement in the proliferation and migration of non-small cell lung cancer cells

Huang

Tan

et al. 2018

Oncol Rep

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“…In addition, in some types of malignant tumors, extranuclear cytoplasmic nucleolin has been shown to correlate with poor prognosis. A similar pattern has been found in lung and esophagus cancers [Qi et al 2015;Xu et al 2016]. Nucleolin has also been shown to play an important role in breast tumors (Moura et al 2012) and to be even associated with tumor angiogenesis [Christian et al 2003].…”

Section: Introductionsupporting

confidence: 68%

Different localization of fluorescently labeled N- and C-termini of nucleolin variants in human glioblastoma cell culture

Panteleev

Pustogarov

Revishchin

et al. 2019

Preprint

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Nucleolus-oriented protein nucleolin plays a significant role in the life of a normal mammalian cell. However, nucleolin is also actively expressed in cells of malignant tumors. At the same time, its expression in different types of cancer is significantly increased compared with normal cells. It is interesting that nucleolin localization often varies in tumor cells, namely in the cytoplasm and on the cell membrane. This fact is considered to be a poor prognostic indicator. This work is devoted to the study of the distribution of nucleolin in human glioblastoma cells. Glioblastoma is one of the most aggressive malignant tumors with an absolutely unfavorable prognosis. These tumors have a high proliferative potential, but in addition they are often characterized by invasive properties. Research on lineage cells does not let to fully study these properties of glioblastoma, since lineage cells are very different from the actual tumor. In our study, we used two primary cell cultures of human glioblastoma with varying degrees of invasiveness of the original tumors. The main interest was directed at studying the localization of nucleolin and its correlation with the invariability of the N- and C-termini of the corresponding protein. Particular attention was paid to the significance of the unaltered C-terminus of nucleolin for its distribution in the cells of transplanted human glioblastoma cultures derived from patient tissues.The aim of this work is to find the relationship between the deformation of the N- or C-terminal sequences of nucleolin and its localization.We showed that in glioblastoma cells, with a high degree of invasion, nucleolin is found in the cytoplasm and close to the cell membrane, and the distribution of nucleolin with undeformed C and N-terminal does not match.

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“…Altogether, nucleolin's biological functions that contribute to cell homeostasis are also responsible for its role in the development of malignant traits under pathological conditions. In this respect, overexpression of nucleolin, and increased localization at the cell membrane, was shown in different cancer cell lines [243][244][245][246][247][248] and endothelial cells 249,250 , as well as in tumors of diverse histological origin [251][252][253][254][255][256][257][258][259] . Nucleolin overexpression contributes to tumorigenesis and cancer progression by supporting cancer cells proliferation and survival, and by promoting invasion and angiogenesis.…”

Section: Nucleolin: a New Perspective On Breast Cancer Needsmentioning

confidence: 98%

Meeting the needs of breast cancer: A nucleolin’s perspective

Gregório

Lacerda

Figueiredo

et al. 2018

Critical Reviews in Oncology/Hematology

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A major challenge in the management of breast cancer disease has been the development of metastases. Finding new molecular targets and the design of targeted therapeutic approaches to improve the overall survival and quality of life of these patients is, therefore, of great importance. Nucleolin, which is overexpressed in cancer cells and tumor-associated blood vessels, have been implicated in various processes supporting tumorigenesis and angiogenesis. Additionally, its overexpression has been demonstrated in a variety of human neoplasias as an unfavorable prognostic factor, associated with a high risk of relapse and low overall survival. Hence, nucleolin has emerged as a relevant target for therapeutic intervention in cancer malignancy, including breast cancer. This review focus on the contribution of nucleolin for cancer disease and on the development of therapeutic strategies targeting this protein. In this respect, it also provides a critical analysis about the potential and pitfalls of nanomedicine for cancer therapy.

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Prognostic significance of nuclear or cytoplasmic nucleolin expression in human non-small cell lung cancer and its relationship with DNA-PKcs

Cited by 34 publications

References 19 publications

Phosphorylation of nucleolin is indispensable to its involvement in the proliferation and migration of non-small cell lung cancer cells

Phosphorylation of nucleolin is indispensable to its involvement in the proliferation and migration of non-small cell lung cancer cells

Different localization of fluorescently labeled N- and C-termini of nucleolin variants in human glioblastoma cell culture

Meeting the needs of breast cancer: A nucleolin’s perspective

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