Persistent activation of <scp>STAT</scp>3 by <scp>PIM</scp>2‐driven positive feedback loop for epithelial‐mesenchymal transition in breast cancer

Uddin, Nizam; Kim, Rae Kwon; Yoo, Kyoungkeun; Kim, Young Heon; Cui, Yan Hong; Kim, In Gyu; Suh, Yongjoon; Lee, Su Jae

doi:10.1111/cas.12668

Cited by 42 publications

(34 citation statements)

References 31 publications

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“…TRPC1-induced AKT and STAT3 activation increase Snail levels through the upregulation of HIF-1α and LC3BII (a hypoxia-induced autophagy marker) [88]. Increased interleukin production (IL-1α and IL-8) due to the action of PIM-3 [89] and PIM-2 as other serine/threonine kinases promotes the metastasis of BC via STAT3 activation and activated STAT3 upregulates PIM-2 expression by forming a positive feedback loop [90]. Furthermore, IL-6/JAK/STAT3 activation induces c-Myc expression through the upregulation of PIM-1 to enhance EMT and stemness [91].…”

Section: Tyrosine and Serine/threonine Kinases As Orchestratorsmentioning

confidence: 99%

Role of JAK/STAT3 Signaling in the Regulation of Metastasis, the Transition of Cancer Stem Cells, and Chemoresistance of Cancer by Epithelial–Mesenchymal Transition

Jin

2020

Cells

298

193

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The JAK/STAT3 signaling pathway plays an essential role in various types of cancers. Activation of this pathway leads to increased tumorigenic and metastatic ability, the transition of cancer stem cells (CSCs), and chemoresistance in cancer via enhancing the epithelial–mesenchymal transition (EMT). EMT acts as a critical regulator in the progression of cancer and is involved in regulating invasion, spread, and survival. Furthermore, accumulating evidence indicates the failure of conventional therapies due to the acquisition of CSC properties. In this review, we summarize the effects of JAK/STAT3 activation on EMT and the generation of CSCs. Moreover, we discuss cutting-edge data on the link between EMT and CSCs in the tumor microenvironment that involves a previously unknown function of miRNAs, and also discuss new regulators of the JAK/STAT3 signaling pathway.

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Section: Tyrosine and Serine/threonine Kinases As Orchestratorsmentioning

confidence: 99%

Role of JAK/STAT3 Signaling in the Regulation of Metastasis, the Transition of Cancer Stem Cells, and Chemoresistance of Cancer by Epithelial–Mesenchymal Transition

Jin

2020

Cells

298

193

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“…Next to activating mutations in ACVR1, the PI3K/Akt pathway can also be upregulated due to mutations in PI3KCA and PIK3RI, encoding subunits of PI3K, which occur in 10-15% of patients (50,51). In addition, BMP induced RAS/MAPK signaling increases transcription of SNAI1/2 and phosphorylates TWIST1 (52,53) and JAK/STAT activation up-regulates all three EMT related transcription factors (54)(55)(56). Indeed, when brainstem progenitor cells were transduced with DIPG associated mutations in ACVR1, SMAD phosphorylation, STAT3 signaling, and mesenchymal marker expression were induced (49).…”

Section: Acvr1mentioning

confidence: 99%

Invaders Exposed: Understanding and Targeting Tumor Cell Invasion in Diffuse Intrinsic Pontine Glioma

et al. 2020

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Diffuse Intrinsic Pontine Glioma (DIPG) is a rare, highly aggressive pediatric brain tumor that originates in the pons. DIPG is untreatable and universally fatal, with a median life expectancy of less than a year. Resection is not an option, due to the anatomical location of the tumor, radiotherapy has limited effect and no chemotherapeutic or targeted treatment approach has proven to be successful. This poor prognosis is partly attributed to the tumor's highly infiltrative diffuse and invasive spread. Thus, targeting the invasive behavior of DIPG has the potential to be of therapeutic value. In order to target DIPG invasion successfully, detailed mechanistic knowledge on the underlying drivers is required. Here, we review both DIPG tumor cell's intrinsic molecular processes and extrinsic environmental factors contributing to DIPG invasion. Importantly, DIPG represents a heterogenous disease and through advances in whole-genome sequencing, different subtypes of disease based on underlying driver mutations are now being recognized. Recent evidence also demonstrates intra-tumor heterogeneity in terms of invasiveness and implies that highly infiltrative tumor subclones can enhance the migratory behavior of neighboring cells. This might partially be mediated by "tumor microtubes," long membranous extensions through which tumor cells connect and communicate, as well as through the secretion of extracellular vesicles. Some of the described processes involved in invasion are already being targeted in clinical trials. However, more research into the mechanisms of DIPG invasion is urgently needed and might result in the development of an effective therapy for children suffering from this devastating disease. We discuss the implications of newly discovered invasive mechanisms for therapeutic targeting and the challenges therapy development face in light of disease in the developing brain.

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“…Similar to MYC, the signal transducer and activator of transcription protein 3 (STAT3) participates in a series of tumorigenic processes including cell proliferation, cell survival, antiapoptosis, angiogenesis, drug resistance, immune evasion, and inflammation . STAT3 is constitutively activated in several human cancers including thyroid, lung, ovarian, breast, colon, and GC . Inhibition of STAT3 has antitumor effects in several human cancer models …”

Section: Introductionmentioning

confidence: 99%

Integrated expression analysis identifies transcription networks in mouse and human gastric neoplasia

Chen

Soutto

Rahman

et al. 2017

Genes Chromosomes & Cancer

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Gastric cancer is a leading cause of cancer-related deaths worldwide. The Tff1 knockout (KO) mouse model develops gastric lesions that include low-grade dysplasia (LGD), high-grade dysplasia (HGD), and adenocarcinomas. In this study, we used Affymetrix microarrays gene expression platforms for analysis of molecular signatures in the mouse stomach (Tff1-KO (LGD) and Tff1 wild-type (normal)) and human gastric cancer tissues and their adjacent normal tissue samples. Combined integrated bioinformatics analysis of mouse and human datasets indicated that 172 genes were consistently deregulated in both human gastric cancer samples and Tff1-KO LGD lesions (P<0.05). Using Ingenuity pathway analysis, these genes mapped to important transcription networks that include MYC, STAT3, β-catenin, RELA, NFATC2, HIF1A, and ETS1 in both human and mouse. Further analysis demonstrated activation of FOXM1 and inhibition of TP53 transcription networks in human gastric cancers but not in Tff1-KO LGD lesions. Using real-time RT-PCR, we validated the deregulated expression of several genes (VCAM1, BGN, CLDN2, COL1A1, COL1A2, COL3A1, EpCAM, IFITM1, MMP9, MMP12, MMP14, PDGFRB, PLAU, and TIMP1) that map to altered transcription networks in both mouse and human gastric neoplasia. Our study demonstrates significant similarities in deregulated transcription networks in human gastric cancer and gastric tumorigenesis in the Tff1-KO mouse model. The data also suggest that activation of MYC, STAT3, RELA, and β-catenin transcription networks could be an early molecular step in gastric carcinogenesis.

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Persistent activation of STAT3 by PIM2‐driven positive feedback loop for epithelial‐mesenchymal transition in breast cancer

Cited by 42 publications

References 31 publications

Role of JAK/STAT3 Signaling in the Regulation of Metastasis, the Transition of Cancer Stem Cells, and Chemoresistance of Cancer by Epithelial–Mesenchymal Transition

Role of JAK/STAT3 Signaling in the Regulation of Metastasis, the Transition of Cancer Stem Cells, and Chemoresistance of Cancer by Epithelial–Mesenchymal Transition

Invaders Exposed: Understanding and Targeting Tumor Cell Invasion in Diffuse Intrinsic Pontine Glioma

Integrated expression analysis identifies transcription networks in mouse and human gastric neoplasia

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