The Biology of K-Ras Signaling Pathways in Pancreatic Cancer

2013 ◽  
pp. 83-115
Author(s):  
Helen Court ◽  
Mark R. Philips ◽  
Dafna Bar-Sagi
Keyword(s):  
Pancreatic Cancer ◽  
Signaling Pathways ◽  
Ras Signaling

scholarly journals Statins induce apoptosis through inhibition of Ras signaling pathways and enhancement of Bim and p27 expression in human hematopoietic tumor cells

Tumor Biology ◽  
2017 ◽  
Vol 39 (10) ◽  
pp. 101042831773494 ◽  
Author(s):  
Daichiro Fujiwara ◽  
Masanobu Tsubaki ◽  
Tomoya Takeda ◽  
Yoshika Tomonari ◽  
Yu-ichi Koumoto ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Tumor Cells ◽  
Ras Signaling

scholarly journals Signaling through mitogen-activated protein kinase and Rac/Rho does not duplicate the effects of activated Ras on skeletal myogenesis.

1997 ◽  
Vol 17 (7) ◽  
pp. 3547-3555 ◽  
Author(s):  
M B Ramocki ◽  
S E Johnson ◽  
M A White ◽  
C L Ashendel ◽  
S F Konieczny ◽  
...  
Keyword(s):  
Map Kinase ◽  
Signaling Pathways ◽  
Transcriptional Activation ◽  
Intracellular Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Ras Signaling ◽  
Negative Effects ◽  
Intracellular Signaling Pathway ◽  
Helix Loop Helix ◽  
Mitogen Activated Protein

The ability of basic helix-loop-helix muscle regulatory factors (MRFs), such as MyoD, to convert nonmuscle cells to a myogenic lineage is regulated by numerous growth factor and oncoprotein signaling pathways. Previous studies have shown that H-Ras 12V inhibits differentiation to a skeletal muscle lineage by disrupting MRF function via a mechanism that is independent of the dimerization, DNA binding, and inherent transcriptional activation properties of the proteins. To investigate the intracellular signaling pathway(s) that mediates the inhibition of MRF-induced myogenesis by oncogenic Ras, we tested two transformation-defective H-Ras 12V effector domain variants for their ability to alter terminal differentiation. H-Ras 12V,35S retains the ability to activate the Raf/MEK/mitogen-activated protein (MAP) kinase cascade, whereas H-Ras 12V,40C is unable to interact directly with Raf-1 yet still influences other signaling intermediates, including Rac and Rho. Expression of each H-Ras 12V variant in C3H10T1/2 cells abrogates MyoD-induced activation of the complete myogenic program, suggesting that MAP kinase-dependent and -independent Ras signaling pathways individually block myogenesis in this model system. However, additional studies with constitutively activated Rac1 and RhoA proteins revealed no negative effects on MyoD-induced myogenesis. Similarly, treatment of Ras-inhibited myoblasts with the MEK1 inhibitor PD98059 revealed that elevated MAP kinase activity is not a significant contributor to the H-Ras 12V effect. These data suggest that an additional Ras pathway, distinct from the well-characterized MAP kinase and Rac/Rho pathways known to be important for the transforming function of activated Ras, is primarily responsible for the inhibition of myogenesis by H-Ras 12V.

scholarly journals mda-7/IL24 kills pancreatic cancer cells by inhibition of the Wnt/PI3K signaling pathways: Identification of IL-20 receptor-mediated bystander activity against pancreatic cancer

2005 ◽  
Vol 11 (5) ◽  
pp. 724-733 ◽  
Author(s):  
Sunil Chada ◽  
Dora Bocangel ◽  
Rajagopal Ramesh ◽  
Elizabeth A. Grimm ◽  
John B. Mumm ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Signaling Pathways ◽  
Pi3k Signaling ◽  
Pancreatic Cancer Cells

Associations of Kras and Hedgehog signaling pathways and their role in pancreatic cancer

Pancreatology ◽  
2014 ◽  
Vol 14 (3) ◽  
pp. S68
Author(s):  
Beatrice Mohelnikova-Duchonova ◽  
Veronika Brynychova ◽  
Ivana Ihnatova ◽  
Martin Oliverius ◽  
Jan Hlavsa ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Signaling Pathways ◽  
Hedgehog Signaling

scholarly journals Oncogenic KRAS engages an RSK1/NF1 pathway to inhibit wild-type RAS signaling in pancreatic cancer

2021 ◽  
Vol 118 (21) ◽  
pp. e2016904118
Author(s):  
Derek K. Cheng ◽  
Tobiloba E. Oni ◽  
Jennifer S. Thalappillil ◽  
Youngkyu Park ◽  
Hsiu-Chi Ting ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Clinical Success ◽  
Treatment Options ◽  
Mass Spectrometry Analysis ◽  
Ductal Adenocarcinoma ◽  
Ras Signaling ◽  
Wild Type ◽  
Feedback Mechanisms ◽  
Spectrometry Analysis ◽  
Pancreatic Cancer Cells

Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy with limited treatment options. Although activating mutations of the KRAS GTPase are the predominant dependency present in >90% of PDAC patients, targeting KRAS mutants directly has been challenging in PDAC. Similarly, strategies targeting known KRAS downstream effectors have had limited clinical success due to feedback mechanisms, alternate pathways, and dose-limiting toxicities in normal tissues. Therefore, identifying additional functionally relevant KRAS interactions in PDAC may allow for a better understanding of feedback mechanisms and unveil potential therapeutic targets. Here, we used proximity labeling to identify protein interactors of active KRAS in PDAC cells. We expressed fusions of wild-type (WT) (BirA-KRAS4B), mutant (BirA-KRAS4BG12D), and nontransforming cytosolic double mutant (BirA-KRAS4BG12D/C185S) KRAS with the BirA biotin ligase in murine PDAC cells. Mass spectrometry analysis revealed that RSK1 selectively interacts with membrane-bound KRASG12D, and we demonstrate that this interaction requires NF1 and SPRED2. We find that membrane RSK1 mediates negative feedback on WT RAS signaling and impedes the proliferation of pancreatic cancer cells upon the ablation of mutant KRAS. Our findings link NF1 to the membrane-localized functions of RSK1 and highlight a role for WT RAS signaling in promoting adaptive resistance to mutant KRAS-specific inhibitors in PDAC.

scholarly journals miR-1266 Contributes to Pancreatic Cancer Progression and Chemoresistance by the STAT3 and NF-κB Signaling Pathways

2018 ◽  
Vol 11 ◽  
pp. 142-158 ◽  
Author(s):  
Xin Zhang ◽  
Dong Ren ◽  
Xianqiu Wu ◽  
Xi Lin ◽  
Liping Ye ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Signaling Pathways ◽  
Cancer Progression
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