Multifaceted roles of TAK1 signaling in cancer

Mukhopadhyay, Himadri; Lee, Nam Y.

doi:10.1038/s41388-019-1088-8

Cited by 66 publications

(73 citation statements)

References 103 publications

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“…TAK1, a member of the MAP kinase kinase kinase (MAP3K) family, was reported to participate in various cellular processes by regulating several signaling pathways, including the p38MAPK and NF-κB pathways, which play critical roles in cell survival and proliferation (25,26). TAK1 overexpression can promote the progression of several cancer types, and is considered a key therapeutic target in multiple types of cancer (27,28). In OC tissues, TAK1 has been found to be overexpressed, and its knockdown suppresses the growth and metastasis of OC cells (15,29,30).…”

Section: Discussionmentioning

confidence: 99%

Long non‑coding RNA MCM3AP‑AS1 drives ovarian cancer progression via the microRNA‑143‑3p/TAK1 axis

et al. 2020

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The long non-coding RNA (lncRNA) MCM3AP antisense 1 (MCM3AP-AS1) has previously been shown to be a key regulator of multiple types of cancer; however whether it is important in the context of ovarian cancer (OC) is uncertain. The present study determined that MCM3AP-AS1 expression in samples from patients with OC was significantly increased, and was associated with tumor stage, presence of lymph node metastases and poorer overall survival. The role of this lncRNA was investigated in vitro, and it was observed that knockdown of MCM3AP-AS1 impaired OC cell proliferation, migration and colony formation. Similarly, it disrupted tumor growth in vivo. The present study further determined that MCM3AP-AS1 was able to directly interact with microRNA (miRNA or miR)-143-3p as a competing endogenous (ce)RNA for this miRNA, thereby regulating the expression of transforming growth factor-β-activated kinase 1 (TAK1), a known target of miR-143-3p in OC. Consistent with this, inhibition of miR-143-3p was sufficient to partially reverse the effects of MCM3AP-AS1-knockdown, which inhibited the proliferation, migration and invasion of OC cells. Together, these results indicate that MCM3AP-AS1 serves as an oncogenic lncRNA in OC by binding to miR-143-3p and thereby promoting TAK1 expression, and suggest that this lncRNA may be a possible target for therapy in OC.

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Section: Discussionmentioning

confidence: 99%

Long non‑coding RNA MCM3AP‑AS1 drives ovarian cancer progression via the microRNA‑143‑3p/TAK1 axis

et al. 2020

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“…MED12 and BAMBI negatively regulate TGF-β receptor. Loss of MED12 or BAMBI induces an EMT-like phenotype in NSCLC, enhancing immunosuppressive effects [ 158 , 159 , 160 ]. Epigallocatechin gallate (EGCG), a food supplement, is a fibroblast-specific, irreversible inhibitor of both lysyl oxidase-like 2 (LOXL2) and TGF-β receptors 1 and 2 (TGBR1/2) [ 161 ].…”

Section: Transforming Growth Factor-β Signaling In K-ras Mutationmentioning

confidence: 99%

Non-Small-Cell Lung Cancer Signaling Pathways, Metabolism, and PD-1/PD-L1 Antibodies

Santarpía

Aguilar

Chaib

et al. 2020

Cancers

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Treatment of advanced (metastatic) non-small-cell lung cancer (NSCLC) is currently mainly based on immunotherapy with antibodies against PD-1 or PD-L1, alone, or in combination with chemotherapy. In locally advanced NSCLC and in early resected stages, immunotherapy is also employed. Tumor PD-L1 expression by immunohistochemistry is considered the standard practice. Response rate is low, with median progression free survival very short in the vast majority of studies reported. Herein, numerous biological facets of NSCLC are described involving driver genetic lesions, mutations ad fusions, PD-L1 glycosylation, ferroptosis and metabolic rewiring in NSCLC and lung adenocarcinoma (LUAD). Novel concepts, such as immune-transmitters and the effect of neurotransmitters in immune evasion and tumor growth, the nascent relevance of necroptosis and pyroptosis, possible new biomarkers, such as gasdermin D and gasdermin E, the conundrum of K-Ras mutations in LUADs, with the growing recognition of liver kinase B1 (LKB1) and metabolic pathways, including others, are also commented. The review serves to charter diverse treatment solutions, depending on the main altered signaling pathways, in order to have effectual immunotherapy. Tumor PDCD1 gene (encoding PD-1) has been recently described, in equilibrium with tumor PD-L1 (encoded by PDCD1LG1). Such description explains tumor hyper-progression, which has been reported in several studies, and poises the fundamental criterion that IHC PD-L1 expression as a biomarker should be revisited.

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“…IRAK4 undergoes autophosphorylation at several residues, including Thr 209 and Thr 387 , and subsequently phosphorylates IRAK1, resulting in the dissociation of IRAK1 and TRAF6 from the active complex [ 94 ]. After dissociation, IRAK1 binds to TAB-1, TAB-2, and TAK-1 (transforming growth factor-β-activated kinase), leading to activation of TAK-1 which phosphorylates the IKK complex (IKKα, IKKβ, and IKKγ), JNK, and the p38 MAPKs [ 95 ].…”

Section: Mechanisms That Activate the Nf-κb Pathway In Pdacmentioning

confidence: 99%

Deciphering the Role of Innate Immune NF-ĸB Pathway in Pancreatic Cancer

Khurana

Dodhiawala

Bulle

et al. 2020

Cancers

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Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers with no effective treatment option. A predominant hallmark of PDAC is the intense fibro-inflammatory stroma which not only physically collapses vasculature but also functionally suppresses anti-tumor immunity. Constitutive and induced activation of the NF-κB transcription factors is a major mechanism that drives inflammation in PDAC. While targeting this pathway is widely supported as a promising therapeutic strategy, clinical success is elusive due to a lack of safe and effective anti-NF-κB pathway therapeutics. Furthermore, the cell type-specific contribution of this pathway, specifically in neoplastic cells, stromal fibroblasts, and immune cells, has not been critically appraised. In this article, we highlighted seminal and recent literature on molecular mechanisms that drive NF-κB activity in each of these major cell types in PDAC, focusing specifically on the innate immune Toll-like/IL-1 receptor pathway. We reviewed recent evidence on the signaling interplay between the NF-κB and oncogenic KRAS signaling pathways in PDAC cells and their collective contribution to cancer inflammation. Lastly, we reviewed clinical trials on agents that target the NF-κB pathway and novel therapeutic strategies that have been proposed in preclinical studies.

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Multifaceted roles of TAK1 signaling in cancer

Cited by 66 publications

References 103 publications

Long non‑coding RNA MCM3AP‑AS1 drives ovarian cancer progression via the microRNA‑143‑3p/TAK1 axis

Long non‑coding RNA MCM3AP‑AS1 drives ovarian cancer progression via the microRNA‑143‑3p/TAK1 axis

Non-Small-Cell Lung Cancer Signaling Pathways, Metabolism, and PD-1/PD-L1 Antibodies

Deciphering the Role of Innate Immune NF-ĸB Pathway in Pancreatic Cancer

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