Therapeutic potential of targeting the Wnt/β‐catenin pathway in the treatment of pancreatic cancer

Javadinia, Seyed Alireza; Shahidsales, Soodabeh; Fanipakdel, Azar; Joudi‐Mashhad, Mona; Mehramiz, Mehrane; Talebian, Sahar; Maftouh, Mona; Mardani, Ramin; Hassanian, Seyed Mahdi; Ferns, Gordon A.

doi:10.1002/jcb.27835

Cited by 42 publications

(42 citation statements)

References 72 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Given that each molecular subtype of breast cancer itself consists of several heterogeneous sub-branches, there is a growing need to discover new biomarkers for predicting the most effective treatment approaches. Since personalized medicine and neoadjuvant chemotherapy have become increasingly popular treatment modalities in different malignancies, it is important to find a marker for early identification of those patients who will benefit from this approach (14)(15)(16). Response to neoadjuvant treatments may be predicted by cell death markers such as cytokeratins (17)(18)(19).…”

Section: Discussionmentioning

confidence: 99%

“…For most patients, this assessment only involves clinical Vol. 15 No.2 Spring 2020 IRANIAN JOURNAL OF PATHOLOGY examination or imaging to track changes in the primary tumor and adjacent lymph nodes (5). Currently, there is no standard method for assessment of the response to neoadjuvant chemotherapy in breast cancer patients; however, several studies have shown that mammography, ultrasound, and MRI examinations may have a role in the prediction of pCR (5)(6)(7)(8).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Changes in Cytokeratin 18 during Neoadjuvant Chemotherapy of Breast Cancer: A Prospective Study

et al. 2020

Self Cite

View full text Add to dashboard Cite

KEYWORDS ABSTRACTBreast carcinoma, Neoadjuvant therapy, Cytokeratin-18, M30 cytokeratin-18 peptide, M65 cytokeratin-18 peptide Scan to discover online Background & Objective: Prediction of response to neoadjuvant treatment is an important part of treatment of patients with breast cancer. This study aimed to assess changes in serum levels of Cytokeratin 18 during neoadjuvant chemotherapy in patients with locally advanced breast cancer and its association with neoadjuvant treatments. Methods: This research was performed on newly diagnosed breast cancer patients referred to Omid Radiotherapy Center and radiotherapy and oncology departments of Emam Reza and Ghaem hospitals, in Mashhad, Iran. Serum levels of M30 and M65 fragments of Cytokeratin 18 were measured before and 24 hours after the first course of neoadjuvant chemotherapy. Changes in serum levels of Cytokeratin 18 and its fragments and their correlation with pathologic response were analyzed.Results: Pre-and post-chemotherapy levels of M30 were respectively 223.9±18.94 and 250.7±23.92 U/L (P=0.24). For M65, these levels were respectively 301.5±313.9 and 330.2±352.2 U/L (P=0.1). Changes in M30 level during chemotherapy in patients with and without pathologic complete response were -20±92.69 and 43.1±106.5, respectively (P=0.1). For M65, these changes were respectively -247±55 and 76±240 (P=0.1). Baseline levels of M30 and M65 had no relation with menopausal status, tumor grade, hormone receptor status, Ki67 expression, molecular subtype, and stage. Conclusion:Our findings showed statistically insignificant changes in the level of Caspase-cleaved-(M30) and uncleaved-(M65) cytokeratin 18 fragments (apoptotic and necrotic indicators, respectively) during neoadjuvant chemotherapy in patients with breast cancer. There was no notable relationship between tumor-related factors and either baseline levels or serum changes of CK18 fragments. Also, there was no correlation between M30/M65 level and pathologic response to neoadjuvant chemotherapy. Main Subjects:Breast Pathology

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Changes in Cytokeratin 18 during Neoadjuvant Chemotherapy of Breast Cancer: A Prospective Study

et al. 2020

Self Cite

View full text Add to dashboard Cite

show abstract

“…Calcipotriol has been identifed as a WNTpathway inhibitor targeting LRP6 (100). Targeting of WNT signaling in cancer is pursued by many ongoing drug discovery programmes (101)(102)(103).…”

Section: Down-regulated Mirs Mediating Metastasis In Pdac Xenograftsmentioning

confidence: 99%

Pancreatic Ductal Adenocarcinoma: MicroRNAs Affecting Tumor Growth and Metastasis in Preclinical In Vivo Models

Weidle

Birzele

Nopora

2019

Cancer Genomics Proteomics

View full text Add to dashboard Cite

“…The role of Wnt signaling in PC carcinogenesis, metastasis, and prognosis has been reported. Its aberrant activation resulting from activating or inactivating mutations in the CTNNB1 gene locus, or in the negative regulators AXIN and APC involving stabilization of β-catenin, and activation of target genes leads to a more aggressive phenotype of PC [23]. Meanwhile, the Wnt signaling drives drug resistance in PC in many ways [24].…”

Section: Introductionmentioning

confidence: 99%

Nigericin Suppresses the Wnt/β-catenin Signaling in Pancreatic Cancer through Targeting pre-miR-374b-PRKCA/HBP1 Axis

Zhi¹,

Li²,

Zhu³

et al. 2020

Preprint

View full text Add to dashboard Cite

Background The polyether antibiotic nigericin has been demonstrated recently to have anti-tumor activity in multiple cancers. But the biochemical basis for its anti-cancer effects has not been fully elucidated. The objective of this study was to investigate the potential mechanisms of nigericin in pancreatic cancer (PC) cells. Methods PC cells were exposed to increasing concentrations of nigericin at different time periods, and the corresponding IC50 values were calculated. Then the effects on the biological functions of PC cells were evaluated. Subsequent experiments including the high-throughput RNA sequencing, qRT-PCR, western blot, TOP/FOP-Flash reporter, Co-Immunoprecipitation and luciferase report assays were employed to reveal the potential mechanisms of nigericin. In addition, the inhibitory effects of nigericin on PC cells were also accessed in the subcutaneous tumor model. Results The data showed that nigericin was extremely sensitive to PC cells, and could influence the abilities of cell proliferation, colony formation, apoptosis, migration and invasion. The results in vitro implied that nigericin suppressed the Wnt/β-catenin signaling by up-regulating PRKCA and HBP1 mRNA expressions. Furthermore, the dual strands of pre-miR-374b were proved to down-regulate the PRKCA and HBP1 expressions coordinately, and over-expression of pre-miR-374b partly antagonized the suppressing effects of PC cells induced by nigericin. Meanwhile, the inhibitory effects of nigericin on PC cells were also confirmed in mice. Conclusion These findings demonstrated that suppressing the Wnt/β-catenin signaling pathway by targeting pre-miR-374b-PRKCA/HBP1 axis might represent a novel molecular mechanism of nigericin in PC. Nigericin remained a candidate for a potential pre-clinical application for PC.

show abstract

Therapeutic potential of targeting the Wnt/β‐catenin pathway in the treatment of pancreatic cancer

Cited by 42 publications

References 72 publications

Changes in Cytokeratin 18 during Neoadjuvant Chemotherapy of Breast Cancer: A Prospective Study

Changes in Cytokeratin 18 during Neoadjuvant Chemotherapy of Breast Cancer: A Prospective Study

Pancreatic Ductal Adenocarcinoma: MicroRNAs Affecting Tumor Growth and Metastasis in Preclinical In Vivo Models

Nigericin Suppresses the Wnt/β-catenin Signaling in Pancreatic Cancer through Targeting pre-miR-374b-PRKCA/HBP1 Axis

Contact Info

Product

Resources

About