Expression of p53 and DR5 in normal and malignant tissues of colorectal cancer: Correlation with advanced stages

Perraud, Aurélie; Akil, Hussein; Nouaille, Michelle; Petit, Daniel; Labrousse, François; Jauberteau, Marie‐Odile; Mathonnet, Muriel

doi:10.3892/or.2011.1404

Cited by 13 publications

(10 citation statements)

References 20 publications

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“…The positive expression of p53 in CRC cases with an SRC component showed a significant association with decreased OS (p = 0.017). Perraud et al 20 also found that p53 was an important marker of advanced tumor stages, and it appeared useful as a prognostic factor to predict recurrence-free survival. Similarly, Liu et al 21 contained 62 (40.5%) patients with p53 positive protein expression.…”

Section: Discussionmentioning

confidence: 99%

The prognostic value of p53 positive in colorectal cancer: A retrospective cohort study

et al. 2017

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This retrospective cohort study aimed to discuss the prognostic value of p53 positive in colorectal cancer. A total of 124 consecutive patients diagnosed with colorectal cancer were evaluated at the National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College from 1 January 2009 to 31 December 2010. The expression of p53 in colorectal cancer was examined by immunohistochemistry. Based on the expression levels of p53, the 124 patients were divided into a p53 positive group and a p53 negative group. In this study, 72 patients were in the p53 positive group and 52 in the p53 negative group. The two groups were well balanced in gender, age, body mass index, American Society of Anesthesiologists scores, and number of lymph nodes harvested. p53 positive was associated with carcinoembryonic antigen ≥5 ng/mL (p = 0.036), gross type (p = 0.037), degree of tumor differentiation (p = 0.026), pathological tumor stage (p = 0.019), pathological node stage (p = 0.004), pathological tumor-node-metastasis stage (p = 0.017), nerve invasion (p = 0.008), and vessel invasion (p = 0.018). Tumor site, tumor size, and pathological pattern were not significantly different between these two groups. Disease-free survival and overall survival in the p53 positive group were significantly shorter than the p53 negative group (p = 0.021 and 0.025, respectively). Colorectal cancer patients with p53 positive tended to be related to a higher degree of malignancy, advanced tumor-node-metastasis stage, and shorter disease-free survival and overall survival. p53 positive was independently an unfavorable prognostic marker for colorectal cancer patients.

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Section: Discussionmentioning

confidence: 99%

The prognostic value of p53 positive in colorectal cancer: A retrospective cohort study

et al. 2017

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“…Deregulation of TRAIL-R expression is frequently observed in tumors where the increased expression of TRAIL-R1 and TRAIL-R2 is correlated with early tumor stage [16]. Conversely down regulation of TRAIL-R has been observed in colorectal cancer patients with more advanced tumor grades [17]. Similarly, loss of membrane-bound TRAIL-R1 and TRAIL-R2 has been correlated, with poor prognosis in pancreatic cancer patients [18].…”

Section: Modulation Of Tumor Necrosis Factor (Tnf)-related Apoptosmentioning

confidence: 99%

Regulation of TRAIL-Receptor Expression by the Ubiquitin-Proteasome System

Sarhan

D’Arcy

Lundqvist

2014

IJMS

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The tumor necrosis factor (TNF)-related apoptosis-inducing ligand- receptor (TRAIL-R) family has emerged as a key mediator of cell fate and survival. Ligation of TRAIL ligand to TRAIL-R1 or TRAIL-R2 initiates the extrinsic apoptotic pathway characterized by the recruitment of death domains, assembly of the death-inducing signaling complex (DISC), caspase activation and ultimately apoptosis. Conversely the decoy receptors TRAIL-R3 and TRAIL-R4, which lack the pro-apoptotic death domain, function to dampen the apoptotic response by competing for TRAIL ligand. The tissue restricted expression of the decoy receptors on normal but not cancer cells provides a therapeutic rational for the development of selective TRAIL-mediated anti-tumor therapies. Recent clinical trials using agonistic antibodies against the apoptosis-inducing TRAIL receptors or recombinant TRAIL have been promising; however the number of patients in complete remission remains stubbornly low. The mechanisms of TRAIL resistance are relatively unexplored but may in part be due to TRAIL-R down-regulation or shedding of TRAIL-R by tumor cells. Therefore a better understanding of the mechanisms underlying TRAIL resistance is required. The ubiquitin-proteasome system (UPS) has been shown to regulate TRAIL-R members suggesting that pharmacological inhibition of the UPS may be a novel strategy to augment TRAIL-based therapies and increase efficacies. We recently identified b-AP15 as an inhibitor of proteasome deubiquitinase (DUB) activity. Interestingly, exposure of tumor cell lines to b-AP15 resulted in increased TRAIL-R2 expression and enhanced sensitivity to TRAIL-mediated apoptosis and cell death in vitro and in vivo. In conclusion, targeting the UPS may represent a novel strategy to increase the cell surface expression of pro-apoptotic TRAIL-R on cancer cells and should be considered in clinical trials targeting TRAIL-receptors in cancer patients.

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“…Accordingly, in situ immunohistochemical analyses of clinical colorectal cancer sections correlated with the tumor stage (stage I-IV), and treatment response demonstrated that p53 and DR5 expression decreased progressively for each stage, suggesting that these proteins are important markers of advanced tumors, and that p53 appears as a prognostic factor to predict recurrencefree survival. 10 It was also shown that inducible silencing of DR5 in mice led to accelerated growth of bioluminescent tumor xenografts and conferred 5-FU-resistance. 11 Similar data have been provided by using tumor cell lines, although conflicting evidences exist postulating DR4, DR5 or CD95 as the regulatory receptor for caspase-8 activation and apoptosis.…”

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confidence: 99%

5-Fluorouracil signaling through a calcium–calmodulin-dependent pathway is required for p53 activation and apoptosis in colon carcinoma cells

et al. 2012

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5-Fluorouracil (5-FU) is an anti-metabolite that is in clinical use for treatment of several cancers. In cells, it is converted into three distinct fluoro-based nucleotide analogs, which interfere with DNA synthesis and repair, leading to genome impairment and, eventually, apoptotic cell death. Current knowledge states that in certain cell types, 5-FU-induced stress is signaling through a p53-dependent induction of tumor necrosis factor-receptor oligomerization required for death-inducing signaling complex formation and caspase-8 activation. Here we establish a role of calcium (Ca 2 þ ) as a messenger for p53 activation in response to 5-FU. Using a combination of pharmacological and genetic approaches, we show that treatment of colon carcinoma cells stimulates entry of extracellular Ca 2 þ through long lasting-type plasma membrane channels, which further directs posttranslational phosphorylation of at least three p53 serine residues (S15, S33 and S37) by means of calmodulin (CaM) activity. Obstructing this pathway by the Ca 2 þ -chelator BAPTA (1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid) or by inhibitors of CaM efficiently reduces 5-FUinduced caspase activities and subsequent cell death. Moreover, ectopic expression of p53 S15A in HCT116 p53 À / À cells confirmed the importance of a Ca 2 þ -CaM-p53 axis in 5-FU-induced extrinsic apoptosis. The fact that a widely used therapeutic drug, such as 5-FU, is operating via this pathway could provide new therapeutic intervention points, or specify new combinatorial treatment regimes.

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Expression of p53 and DR5 in normal and malignant tissues of colorectal cancer: Correlation with advanced stages

Cited by 13 publications

References 20 publications

The prognostic value of p53 positive in colorectal cancer: A retrospective cohort study

The prognostic value of p53 positive in colorectal cancer: A retrospective cohort study

Regulation of TRAIL-Receptor Expression by the Ubiquitin-Proteasome System

5-Fluorouracil signaling through a calcium–calmodulin-dependent pathway is required for p53 activation and apoptosis in colon carcinoma cells

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