ArticleCellular oncology (Dordrecht, Netherlands)2020
Downregulation of beta-catenin in chemo-tolerant TNBC through changes in receptor and antagonist profiles of the WNT pathway: Clinical and prognostic implications.
Article in Cellular oncology (Dordrecht, Netherlands), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 13 citations in OpenAlex.
- Down-regulation of FA-BRCA Pathway in Cervical Carcinoma Gradually Reversed During the Development of Chemo-tolerance: Clinical Implications.Reproductive sciences (Thousand Oaks, Calif.) · 2024Article
- Dkk1 as a Prognostic Marker for Neoadjuvant Chemotherapy Response in Breast Cancer Patients.Cancers · 2024Article
- Discovery of a first-in-class ANXA3 degrader for the treatment of triple-negative breast cancer.Acta pharmaceutica Sinica. B · 2023Article
- High nuclear expression of DNMT1 in correlation with inactivation of TET1 portray worst prognosis among the cervical carcinoma patients: clinical implications.Journal of molecular histology · 2023Article
- Targeting regulated cell death (RCD) with small-molecule compounds in triple-negative breast cancer: a revisited perspective from molecular mechanisms to targeted therapies.Journal of hematology & oncology · 2022Review
- High nuclear expression of HIF1α, synergizing with inactivation of LIMD1 and VHL, portray worst prognosis among the bladder cancer patients: association with arsenic prevalence.Journal of cancer research and clinical oncology · 2021Article
- Upregulation of miRNA-1228-3p alleviates TGF-β-induced fibrosis in renal tubular epithelial cells.Histology and histopathology · 2020Article
Corrections and comments
- Retraction · 2025-01-21Concerns/Issues about Data · Duplication of Data · Duplication of/in Image · Euphemisms for Duplication · Investigation by Journal/Publisher · Objections by Author(s) · Unreliable Data ·
- Retracted
Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
purposeIn approximately 30% of triple-negative breast cancer (TNBC) patients a complete pathological response is achieved. However, after neo-adjuvant chemotherapy treatment (NACT) residual tumour cells can be intrinsically resistant to chemotherapy. In this study, associations of the WNT/beta-catenin pathway with chemo-tolerance of NACT treated TNBC patients were compared to that of pre-treatment TNBC patients.
methodsExpression analyses were performed in both pre-treatment and NACT treated TNBC samples using immunohistochemistry and qRT-PCR, along with DNA copy number variation (CNV) and promoter methylation analyses to elucidate the mechanism(s) underlying chemo-tolerance. In addition, in vitro validation experiments were performed in TNBC cells followed by in vivo clinicopathological correlation analyses.
resultsA reduced expression (41.1%) of nuclear beta-catenin together with a low proliferation index was observed in NACT samples, whereas a high expression (59.0%) was observed in pre-treatment samples. The reduced nuclear expression of beta-catenin in the NACT samples showed concordance with reduced expression levels (47-52.9%) of its associated receptors (FZD7 and LRP6) and increased expression levels (35.2-41.1%) of its antagonists (SFRP1, SFRP2, DKK1) compared to those in the pre-treatment samples. The expression levels of the receptors showed no concordance with its respective gene copy number/mRNA expression statuses, regardless treatment. Interestingly, however, significant increases in promoter hypomethylation of the antagonists were observed in the NACT samples compared to the pre-treatment samples. Similar expression patterns of the antagonists, receptors and beta-catenin were observed in the TNBC-derived cell line MDA-MB-231 using the anthracyclines doxorubicin and nogalamycin, suggesting the importance of promoter hypomethylation in chemotolerance. NACT patients showing reduced receptor and/or beta-catenin expression levels and high antagonist expression levels exhibited a comparatively better prognosis than the pre-treatment patients.
conclusionsOur data suggest that reduced nuclear expression of beta-catenin in NACT TNBC samples, due to downregulation of its receptors and upregulation of its antagonists through promoter hypomethylation of the WNT pathway, plays an important role in chemo-tolerance.
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