Cellular senescence in oral cancer and precancer and treatment implications: A review

Campo‐Trapero, Julián; Cano‐Sánchez, Jorge; Palacios-Sánchez, Begoña; Llamas-Martínez, Silvia; Muzio, Lorenzo Lo; Bascones-Martínez, A.

doi:10.1080/02841860802183612

Cited by 31 publications

(23 citation statements)

References 49 publications

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“…A pro-senescence approach to cancer therapy is an attractive alternative approach to chemotherapeutic strategies [12]. However, abundant reports indicate that cellular senescence occurs in the pre-malignant stage of oral squamous cell carcinoma (OSCC) but is lost once malignant transformation has occurred [13,14,15,16,17]. In contrast, stress or oncogene-induced senescence (OIS) also reported in OSCC and indicated that OIS and its markers could play a role in OSCC tumor progression [18,19,20].…”

Section: Introductionmentioning

confidence: 99%

RNA-Binding Protein FXR1 Regulates p21 and TERC RNA to Bypass p53-Mediated Cellular Senescence in OSCC

et al. 2016

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RNA-binding proteins (RBP) regulate numerous aspects of co- and post-transcriptional gene expression in cancer cells. Here, we demonstrate that RBP, fragile X-related protein 1 (FXR1), plays an essential role in cellular senescence by utilizing mRNA turnover pathway. We report that overexpressed FXR1 in head and neck squamous cell carcinoma targets (G-quadruplex (G4) RNA structure within) both mRNA encoding p21 (Cyclin-Dependent Kinase Inhibitor 1A (CDKN1A, Cip1) and the non-coding RNA Telomerase RNA Component (TERC), and regulates their turnover to avoid senescence. Silencing of FXR1 in cancer cells triggers the activation of Cyclin-Dependent Kinase Inhibitors, p53, increases DNA damage, and ultimately, cellular senescence. Overexpressed FXR1 binds and destabilizes p21 mRNA, subsequently reduces p21 protein expression in oral cancer cells. In addition, FXR1 also binds and stabilizes TERC RNA and suppresses the cellular senescence possibly through telomerase activity. Finally, we report that FXR1-regulated senescence is irreversible and FXR1-depleted cells fail to form colonies to re-enter cellular proliferation. Collectively, FXR1 displays a novel mechanism of controlling the expression of p21 through p53-dependent manner to bypass cellular senescence in oral cancer cells.

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Section: Introductionmentioning

confidence: 99%

RNA-Binding Protein FXR1 Regulates p21 and TERC RNA to Bypass p53-Mediated Cellular Senescence in OSCC

et al. 2016

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“…As has been suggested, OIS could have a role in the development of pre-malignant lesions, explaining p16 Ink4a overexpression in benign and pre-malignant lesions (Zhang et al, 2006;Campo-Trapero et al, 2008). However, p16 Ink4a should stop proliferation in cells with a properly functioning p16 Ink4a -Rb pathway.…”

Section: Subcellular Location Of P16 Ink4a Overexpressionmentioning

confidence: 95%

p16Ink4a overexpression in cancer: a tumor suppressor gene associated with senescence and high-grade tumors

et al. 2011

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p16 Ink4a is a protein involved in regulation of the cell cycle. Currently, p16 Ink4a is considered a tumor suppressor protein because of its physiological role and downregulated expression in a large number of tumors. Intriguingly, overexpression of p16 Ink4a has also been described in several tumors. This review attempts to elucidate when and why p16 Ink4a overexpression occurs, and to suggest possible implications of p16 Ink4a in the diagnosis, prognosis and treatment of cancer.

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“…While there are some limitations on the use of activity assays for this enzyme, this marker can be sensitively detected by histochemical staining in most senescent cells and tissue. In addition to negative regulators of the cell cycle, such as p15 IK4b (p15), p16 INK4a (p16), ARF and p21 Cip1/Waf1 (p21), differentiated embryonic chondrocyte expressed-1 (DEC1) and decoy death receptor-2 (DCR2) have been identified as senescence indicators (24,25). Recently, our group also identified cathepsin D and eukaryotic elongation factor 1 as promising markers for the detection of cellular senescence induced by a variety of treatments (26).…”

Section: Cellular Senescence: a Fundamental Aspect Of Cell Biologymentioning

confidence: 99%

Exploiting tumor cell senescence in anticancer therapy

Lee¹,

Lee²

2014

BMB Reports

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Cellular senescence is a physiological process of irreversible cell-cycle arrest that contributes to various physiological and pathological processes of aging. Whereas replicative senescence is associated with telomere attrition after repeated cell division, stress-induced premature senescence occurs in response to aberrant oncogenic signaling, oxidative stress, and DNA damage which is independent of telomere dysfunction. Recent evidence indicates that cellular senescence provides a barrier to tumorigenesis and is a determinant of the outcome of cancer treatment. However, the senescence-associated secretory phenotype, which contributes to multiple facets of senescent cancer cells, may influence both cancer-inhibitory and cancer-promoting mechanisms of neighboring cells. Conventional treatments, such as chemo- and radiotherapies, preferentially induce premature senescence instead of apoptosis in the appropriate cellular context. In addition, treatment-induced premature senescence could compensate for resistance to apoptosis via alternative signaling pathways. Therefore, we believe that an intensive effort to understand cancer cell senescence could facilitate the development of novel therapeutic strategies for improving the efficacy of anticancer therapies. This review summarizes the current understanding of molecular mechanisms, functions, and clinical applications of cellular senescence for anticancer therapy. [BMB Reports 2014; 47(2): 51-59]

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Cellular senescence in oral cancer and precancer and treatment implications: A review

Abstract: In the short term, the study of this mechanism may yield valuable data for the management of oral cancer and precancer, for which no effective diagnostic or prognostic markers are yet available.

Cited by 31 publications

References 49 publications

RNA-Binding Protein FXR1 Regulates p21 and TERC RNA to Bypass p53-Mediated Cellular Senescence in OSCC

RNA-Binding Protein FXR1 Regulates p21 and TERC RNA to Bypass p53-Mediated Cellular Senescence in OSCC

p16Ink4a overexpression in cancer: a tumor suppressor gene associated with senescence and high-grade tumors

Exploiting tumor cell senescence in anticancer therapy

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