Abstract A63: Role of the metastasis suppressor, NDRG1, in regulating the EGFR and ErbB family of receptors and its effects on key oncogenic signaling pathways in pancreatic cancer

p21-Activated kinase 1 (PAK1) has attracted much attention as a potential therapeutic target due to its central role in many oncogenic signaling pathways, its frequent dysregulation in cancers and neurological disorders, and its tractability as a target for small-molecule inhibition. To date, several PAK1-targeting compounds have been developed as preclinical agents, including one that has been evaluated in a clinical trial. A series of ATP-competitive inhibitors, allosteric inhibitors and peptide inhibitors with distinct biochemical and pharmacokinetic properties represent useful laboratory tools for studies on the role of PAK1 in biology and in disease contexts, and could lead to promising therapeutic agents. Given the central role of PAK1 in vital signaling pathways, future clinical development of PAK1 inhibitors will require careful investigation of their safety and efficacy.

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WNT Signaling: an Emerging Mediator of Cancer Cell Metabolism?

Molecular and Cellular Biology ◽

10.1128/mcb.00992-14 ◽

2014 ◽

Vol 35 (1) ◽

pp. 2-10 ◽

Cited By ~ 83

Author(s):

Victoria Sherwood

Keyword(s):

Wnt Signaling ◽

Signaling Pathways ◽

Cancer Cell ◽

Cancer Metabolism ◽

Cell Metabolism ◽

Critical Role ◽

Oncogenic Signaling ◽

Cancer Cell Metabolism ◽

Oncogenic Signaling Pathways

WNT signaling was discovered in tumor models and has been recognized as a regulator of cancer development and progression for over 3 decades. Recent work has highlighted a critical role for WNT signaling in the metabolic homeostasis of mammals, where its misregulation has been heavily implicated in diabetes. While the majority of WNT metabolism research has focused on nontransformed tissues, the role of WNT in cancer metabolism remains underinvestigated. Cancer is also a metabolic disease where oncogenic signaling pathways regulate energy production and macromolecular synthesis to fuel rapidly proliferating tumors. This review highlights the emerging evidence for WNT signaling in the reprogramming of cancer cell metabolism and examines the role of these signaling pathways as mediators of tumor bioenergetics.

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Regulation of Canonical Oncogenic Signaling Pathways in Cancer via DNA Methylation

Cancers ◽

10.3390/cancers12113199 ◽

2020 ◽

Vol 12 (11) ◽

pp. 3199

Author(s):

Jennifer Lu ◽

Premila Wilfred ◽

Darren Korbie ◽

Matt Trau

Keyword(s):

Dna Methylation ◽

Signaling Pathways ◽

Biomarker Discovery ◽

Oncogenic Signaling ◽

Tissue Samples ◽

Epigenetic Biomarkers ◽

Differentially Methylated Genes ◽

Oncogenic Signaling Pathways ◽

Integration Analysis

Disruption of signaling pathways that plays a role in the normal development and cellular homeostasis may lead to the dysregulation of cellular signaling and bring about the onset of different diseases, including cancer. In addition to genetic aberrations, DNA methylation also acts as an epigenetic modifier to drive the onset and progression of cancer by mediating the reversible transcription of related genes. Although the role of DNA methylation as an alternative driver of carcinogenesis has been well-established, the global effects of DNA methylation on oncogenic signaling pathways and the presentation of cancer is only emerging. In this article, we introduced a differential methylation parsing pipeline (MethylMine) which mined for epigenetic biomarkers based on feature selection. This pipeline was used to mine for biomarkers, which presented a substantial difference in methylation between the tumor and the matching normal tissue samples. Combined with the Data Integration Analysis for Biomarker discovery (DIABLO) framework for machine learning and multi-omic analysis, we revisited the TCGA DNA methylation and RNA-Seq datasets for breast, colorectal, lung, and prostate cancer, and identified differentially methylated genes within the NRF2-KEAP1/PI3K oncogenic pathway, which regulates the expression of cytoprotective genes, that serve as potential therapeutic targets to treat different cancers.

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Abstract 2242: Inhibition of acetyl-CoA carboxylase attenuates lipidation and activity of oncogenic signaling pathways in pancreatic cancer

10.1158/1538-7445.am2015-2242 ◽

2015 ◽

Author(s):

Elissaveta Petrova ◽

Arne Scholz ◽

Andrea Sturz ◽

Juliane Paul ◽

Franziska Siegel ◽

...

Keyword(s):

Pancreatic Cancer ◽

Signaling Pathways ◽

Acetyl Coa Carboxylase ◽

Oncogenic Signaling ◽

Acetyl Coa ◽

Oncogenic Signaling Pathways

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MALAT1 as a Versatile Regulator of Cancer: Overview of the updates from Predatory role as Competitive Endogenous RNA to Mechanistic In-sights

Current Cancer Drug Targets ◽

10.2174/1568009620999200730183110 ◽

2020 ◽

Vol 20 ◽

Author(s):

Ammad Ahmad Farooqi ◽

Evangelia Legaki ◽

Maria Gazouli ◽

Silvia Rinaldi ◽

Rossana Berardi

Keyword(s):

Molecular Biology ◽

Detailed Analysis ◽

Signaling Pathways ◽

Individualized Medicine ◽

Signaling Cascades ◽

Oncogenic Signaling ◽

Non Coding Rnas ◽

Oncogenic Signaling Pathways ◽

Competitive Endogenous Rna

: Central dogma of molecular biology has remained cornerstone of classical molecular biology but serendipitous discovery of microRNAs (miRNAs) in nematodes paradigmatically shifted our current understanding of the intricate mech-anisms which occur during transitions from transcription to translation. Discovery of miRNA captured tremendous attention and appreciation and we had witnessed an explosion in the field of non-coding RNAs. Ground-breaking discoveries in the field of non-coding RNAs have helped in better characterization of microRNAs and long non-coding RNAs (LncRNAs). There is an ever-increasing list of miRNA targets which are regulated by MALAT1 to stimulate or repress expression of tar-get genes. However, in this review our main focus is to summarize mechanistic insights related to MALAT1-mediated regu-lation of oncogenic signaling pathways. We have discussed how MALAT1 modulated TGF/SMAD and Hippo pathways in various cancers. We have also comprehensively summarized how JAK/STAT and Wnt/β-catenin pathways stimulated MALAT1 expression and consequentially how MALAT1 potentiated these signaling cascades to promote cancer. MALAT1 research has undergone substantial broadening however, there is still a need to identify additional mechanisms. MALAT1 is involved in multi-layered regulation of multiple transduction cascades and detailed analysis of different pathways will be helpful in getting a step closer to individualized medicine.

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The m6A RNA methylation regulates oncogenic signaling pathways driving cell malignant transformation and carcinogenesis

Molecular Cancer ◽

10.1186/s12943-021-01356-0 ◽

2021 ◽

Vol 20 (1) ◽

Author(s):

Mohammad Burhan Uddin ◽

Zhishan Wang ◽

Chengfeng Yang

Keyword(s):

Signaling Pathways ◽

Malignant Transformation ◽

Noncoding Rna ◽

Rna Modification ◽

Oncogenic Signaling ◽

Aberrant Expression ◽

Rna Methylation ◽

Rna Molecules ◽

M6a Rna Methylation ◽

Oncogenic Signaling Pathways

AbstractThe m6A RNA methylation is the most prevalent internal modification in mammalian mRNAs which plays critical biological roles by regulating vital cellular processes. Dysregulations of the m6A modification due to aberrant expression of its regulatory proteins are frequently observed in many pathological conditions, particularly in cancer. Normal cells undergo malignant transformation via activation or modulation of different oncogenic signaling pathways through complex mechanisms. Accumulating evidence showing regulation of oncogenic signaling pathways at the epitranscriptomic level has added an extra layer of the complexity. In particular, recent studies demonstrated that, in many types of cancers various oncogenic signaling pathways are modulated by the m6A modification in the target mRNAs as well as noncoding RNA transcripts. m6A modifications in these RNA molecules control their fate and metabolism by regulating their stability, translation or subcellular localizations. In this review we discussed recent exciting studies on oncogenic signaling pathways that are modulated by the m6A RNA modification and/or their regulators in cancer and provided perspectives for further studies. The regulation of oncogenic signaling pathways by the m6A modification and its regulators also render them as potential druggable targets for the treatment of cancer.

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