Chemoradiotherapy Resistance in Colorectal Cancer Cells is Mediated by Wnt/{beta}-catenin Signaling

Activation of Wnt/β-catenin signaling plays a central role in the development and progression of colorectal cancer. The Wnt-transcription factor, TCF7L2, is overexpressed in primary rectal cancers that are resistant to chemoradiotherapy and TCF7L2 mediates resistance to chemoradiotherapy. However, it is unclear whether the resistance is mediated by a TCF7L2 inherent mechanism or Wnt/β-catenin signaling in general. Here, inhibition of β-catenin by siRNAs or a small-molecule inhibitor (XAV-939) resulted in sensitization of colorectal cancer cells to chemoradiotherapy. To investigate the potential role of Wnt/β-catenin signaling in controlling therapeutic responsiveness, nontumorigenic RPE-1 cells were stimulated with Wnt-3a, a physiologic ligand of Frizzled receptors, which increased resistance to chemoradiotherapy. This effect could be recapitulated by overexpression of a degradation-resistant mutant of β-catenin (S33Y), also boosting resistance of RPE-1 cells to chemoradiotherapy, which was, conversely, abrogated by siRNA-mediated silencing of β-catenin. Consistent with these findings, higher expression levels of active β-catenin were observed as well as increased TCF/LEF reporter activity in SW1463 cells that evolved radiation resistance due to repeated radiation treatment. Global gene expression profiling identified several altered pathways, including PPAR signaling and other metabolic pathways, associated with cellular response to radiati...
Source: Molecular Cancer Research - Category: Cancer & Oncology Authors: Tags: Cell Death and Survival Source Type: research

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Conclusions: High MRE11 expression is an independent prognostic marker in LSCRC and enhanced prognostic potency of combining high MRE11 with high TIICs in LSCRC, mainly due to differential immune signaling activated by MRE11 in RSCC and LSCRC, respectively.
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Authors: Li C, Zuo D, Liu T, Yin L, Li C, Wang L Abstract Objective: To assess the association between MUC expression levels in colorectal cancer (CRC) tissues and prognosis and investigate the associations between MUC expression levels and CRC clinicopathological characteristics. Methods: The PubMed, Embase, Cochrane Library, and Web of Science databases were searched from inception through September 13, 2019, to identify studies investigating the association between MUC expression levels in CRC tissues and prognosis. Pooled hazard ratios (HRs) or odds ratio (ORs) with 95% confidence intervals (CIs) were used ...
Source: Gastroenterology Research and Practice - Category: Gastroenterology Tags: Gastroenterol Res Pract Source Type: research
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Source: Journal of General Internal Medicine - Category: Internal Medicine Source Type: research
ConclusionsPatients undergoing PR operations were more likely to have had major complications than were patients who underwent AC procedures; unfortunately no improvement in the rate of these complications or in mortality occurred. Perhaps the significant reduction in length of stay is due in part to an increased prevalence of minimally invasive surgery and/or enhanced recovery protocols. Data were found to be lacking within NSQIP for several important variables including key oncologic data, stratification by surgical volume, and patient geographic location. We anticipate that the NAPRC should help improve PR surgical and ...
Source: The American Journal of Surgery - Category: Surgery Source Type: research
This tenth report of the audit includes data on over 30,000 patients diagnosed with bowel cancer between 01 April 2017 and 31 March 2018. For the first time, indicators of return to theatre and robotic surgery are reported and the measure of adjuvant chemotherapy for stage III colon cancer is reported at trust/hospital level in England. The report discusses several key findings for care pathways, surgical care, survival, rectal cancer and National Cancer Registry data.
Source: Current Awareness Service for Health (CASH) - Category: Consumer Health News Source Type: news
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Source: European Journal of Surgical Oncology (EJSO) - Category: Surgery Source Type: research
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Source: Diseases of the Colon and Rectum - Category: Gastroenterology Tags: Original Contributions: Colorectal Cancer Source Type: research
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Source: Diseases of the Colon and Rectum - Category: Gastroenterology Tags: Original Contributions: Colorectal Cancer Source Type: research
Abstract During the last two decades a neoadjuvant treatment concept has been established for an increasing number of malignant tumors of the gastrointestinal tract; however, these concepts are still subject to a constant change concerning the indications and type of treatment. A prime example for this is rectal cancer. The rate of local recurrence in particular was significantly reduced by neoadjuvant therapy but until now it has not been possible to validly show an improvement in overall or disease-free survival. At the beginning of the millennium it was recommended to treat every rectal carcinoma...
Source: Der Chirurg - Category: Surgery Authors: Tags: Chirurg Source Type: research
Conclusion: Our work contributes to the elucidation of the predictive value of DNp73 expression in rectal cancer patients who were given preoperative radiotherapy. Mathematical properties of fuzzy weighted recurrence networks of immunohistochemistry images are not only able to show the predictive factor of DNp73 expression in the patients, but also reveal the identification of non-effective application of radiotherapy to those who had poor overall survival outcome.
Source: Frontiers in Physiology - Category: Physiology Source Type: research
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