CDK14/β‐catenin/TCF4/miR‐26b positive feedback regulation modulating pancreatic cancer cell phenotypes in vitro and tumor growth in mice model in vivo

2021 ◽  
Author(s):  
Yunpeng Sun ◽  
Pengfei Wang ◽  
Qiyu Zhang ◽  
Huanhuan Wu
Keyword(s):  
Pancreatic Cancer ◽  
Tumor Growth ◽  
Cancer Cell ◽  
Positive Feedback ◽  
Pancreatic Cancer Cell ◽  
Feedback Regulation ◽  
Mice Model ◽  
Cell Phenotypes

scholarly journals TGF-βRII knock-down promotes tumor growth and chemoresistance to gemcitabine of pancreatic cancer cells via phosphorylation of STAT3

2018 ◽  
Author(s):  
Vincent Drubay ◽  
Nicolas Skrypek ◽  
Lucie Cordiez ◽  
Romain Vasseur ◽  
Céline Schulz ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Tumor Growth ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Pancreatic Cancer Cell ◽  
Locally Advanced ◽  
Pancreatic Cancer Cells ◽  
The Impact

AbstractPancreatic adenocarcinoma (PDAC) is one of the most deadly cancers in the western countries because of a lack of early diagnostic markers and efficient therapeutics. At the time of diagnosis, more than 80% of patients have metastasis or locally advanced cancer and are therefore not eligible for surgical resection. Pancreatic cancer cell also harbour a high resistance to chemotherapeutic drugs such as gemcitabine that is one of the main palliative treatment for PDAC.TGF-β possesses both tumor-suppressive and oncogenic activities in pancreatic cancer. TGF-β signalling pathway plays complex role during carcinogenesis by initially inhibiting epithelial growth and later promoting the progression of advanced tumors and thus emerged as tumor suppressor pathway. TGF-β binds to its receptor TGF-βRII and activates different pathways: canonical pathway involving the Smad proteins and alternative pathways such as MAPKs. Smad4 is mutated in 50-80% of PDAC. Mutations of TGF-βRII also occurs (5-10%). In order to decipher the role of TGF-β in carcinogenesis and chemoresistance, we decided to characterize the knocking down of TGF-βRII that is the first actor of TGF-β signalling. We developed pancreatic cancer cell lines stably invalidated for TGF-βRII and studied the impact on biological properties of pancreatic cancer cells both in vitro and in vivo. We show that TGF-βRII silencing alters tumor growth and migration as well as resistance to. TGF-βRII silencing also leads to S727 STAT3 and S-63 c-Jun phosphorylation, decrease of MRP3 and increase of MRP4 ABC transporter expression and induction of a partial EMT phenotype.In the future, the better understanding TGF-β signaling pathways and underlying cellular mechanisms in chemoresistance to gemcitabine may bring new therapeutic tools to clinicians.

scholarly journals Deferasirox, an oral iron chelator, with gemcitabine synergistically inhibits pancreatic cancer cell growth in vitro and in vivo

Oncotarget ◽  
2018 ◽  
Vol 9 (47) ◽  
pp. 28434-28444 ◽  
Author(s):  
Shuhei Shinoda ◽  
Seiji Kaino ◽  
Shogo Amano ◽  
Hirofumi Harima ◽  
Toshihiko Matsumoto ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cell Growth ◽  
Cancer Cell ◽  
Pancreatic Cancer Cell ◽  
Iron Chelator ◽  
Oral Iron ◽  
Cancer Cell Growth ◽  
Oral Iron Chelator

Cordycepin inhibits pancreatic cancer cell growth in vitro and in vivo via targeting FGFR2 and blocking ERK signaling

2020 ◽  
Vol 18 (5) ◽  
pp. 345-355
Author(s):  
Xue-Ying LI ◽  
Homng TAO ◽  
Can JIN ◽  
Zhen-Yun DU ◽  
Wen-Feng LIAO ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cell Growth ◽  
Cancer Cell ◽  
Pancreatic Cancer Cell ◽  
Erk Signaling ◽  
Cancer Cell Growth

Inhibition of cMET in an experimental model of pancreatic cancer.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 185-185
Author(s):  
Sven A. Lang ◽  
Franziska Brandes ◽  
Edward K. Geissler
Keyword(s):  
Pancreatic Cancer ◽  
Tumor Growth ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Pancreatic Cancer Cell ◽  
Cancer Cell Lines ◽  
Human Pancreatic Cancer ◽  
Oncogenic Signaling

185 Background: In human pancreatic cancer, expression of cMET is associated with poor survival. So far, activation/expression of cMET by hepatocyte growth factor (HGF) has been shown to induce proliferation and motility in cancer cells. Therefore, we hypothesized that inhibition of cMET in human pancreatic cancer cell lines impairs oncogenic signaling and tumor growth. Methods: Pancreatic cancer cell lines (HPAF-II, MiaPaCa2, L3.6pl, BxPC3, Panc02) and the cMET inhibitor INC280 (Novartis Oncology, Basel) were used. MiaPaCa2 and L3.6pl pancreatic cancer cells were grown with gemcitabine up to 500 and 250 nM, respectively (then called MiaPaCa2(G500) and L3.6pl(G250)). MTT and Boyden Chamber assays were used to determine effects of INC280 on growth and motility of cells in vitro. Expression of growth factor receptors, activation of signaling intermediates and expression of transcription factors were assessed by Western blotting. Finally, in vitro results were validated in an orthotopic tumor model using L3.6pl pancreatic cancer cell line. Results: All pancreatic cancer cell lines showed expression of cMET. In vitro treatment of cancer cells with INC280 led to a minor, dose-dependent inhibition of growth even when cells were supplemented with HGF. In contrast, migration assays showed a significant reduction of cancer cell motility upon INC280 when cells were stimulated with HGF (P<0.05). Regarding oncogenic signaling, INC280 led to inhibition of HGF-induced phosphorylation of AKT, ERK and FAK. In addition, c-Myc expression was diminished in cancer cells. Interestingly, gemcitabine resistant cell line MiaPaCa2(G500) showed higher cMET expression levels compared to the normal MiaPaCa2. Stimulation of MiaPaCa2(G500) with HGF led to strong induction of oncogenic signaling and tumor cell motility, an effect that was significantly diminished by INC280. Moreover, results from in vivo experiments show that therapy with INC280 (10 mg/kg/d) significantly reduces tumor growth as determined by final tumor weight (P<0.05). Conclusions: In pancreatic cancer cell lines, targeting cMET with INC280 abrogates oncogenic signaling in vitro and impairs tumor growth in vivo. Therefore, the concept of cMET inhibition warrants further preclinical evaluation.

EXPRESSION OF FGFR1-IIIB INHIBITS PANCREATIC CANCER CELL GROWTH IN VITRO AND IN VIVO

Pancreas ◽  
2006 ◽  
Vol 33 (4) ◽  
pp. 475
Author(s):  
M. Kornmann ◽  
S. Zhou ◽  
D. Henne-Bruns ◽  
M. Korc ◽  
M. Bachem ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cell Growth ◽  
Cancer Cell ◽  
Pancreatic Cancer Cell ◽  
Cancer Cell Growth

Signal transducer and activator of transcription 5b (STAT5b) as a novel target for anti-neoplastic therapy in human pancreatic cancer.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 217-217
Author(s):  
C. Moser ◽  
P. Ruemle ◽  
H. Schenk ◽  
E. K. Geissler ◽  
H. J. Schlitt ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Tumor Growth ◽  
Cell Motility ◽  
Cancer Cell ◽  
Human Pancreatic Cancer ◽  
Signal Transducer ◽  
Tumor Vascularization ◽  
Knock Down

217 Background: Activation of signal transducer and activator of transcription 5b (STAT5b) has been associated with tumor growth and metastases in various tumor entities. A number of cytokines, growth factors, and oncogenes that can induce STAT5b activity are also implicated in pancreatic cancer growth and metastases. Hence, we sought to determine STAT5b expression in human pancreatic cancer specimen and effects of selective STAT5b inhibition on pancreatic cancer cells. Methods: Expression of STAT5b in human pancreatic adenocarcinomas was determined by immunohistochemistry. For in vitro experiments, human pancreatic cancer cell lines (BxPC-3, HPAF-II, L3.6pl) were used. Cancer cells were transfected with STAT5b shRNA plasmid to create stable STAT5b knock-down. Effects of STAT5b inhibition on growth and motility of tumor cells was investigated by MTT and modified Boyden chamber assays. In vivo effects of STAT5b blockade were determined in subcutaneous mouse model. Results: Nuclear expression of STAT5b was detected in 42/80 human pancreatic adenocarcinomas. In human cancer cell lines, stable knock-down of STAT5b had no effect on growth of tumor cells in vitro. However, tumor cell motility was significantly reduced upon STAT5b blockade (p<0.05). Moreover, expression of various signaling intermediates and transcription factors including c-myc was impaired upon STAT5b knock-down. In a subcutaneous tumor model, inhibition of STAT5b led to significantly reduced tumor growth (p<0.05) which was also reflected by final tumor weights (p<0.05). Furthermore, as revealed by immunohistochemistry, blockade of STAT5b significantly reduced tumor vascularization in vivo (p<0.05). Conclusions: STAT5b is expressed in human pancreatic adenocarcinomas. Blockade of STAT5b impairs cancer cell motility in vitro, suggesting antimetastatic potential. Moreover, inhibition of STAT5b significantly reduces tumor growth and tumor vascularization in vivo. Hence, STAT5b might be an interesting target for antineoplastic therapy in human pancreatic cancer. No significant financial relationships to disclose.

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