Abstract：
:KRAS oncogenic mutations are widespread in lung cancer and, because direct targeting of KRAS has proven to be challenging, KRAS-driven cancers lack effective therapies. One alternative strategy for developing KRAS targeted therapies is to identify downstream targets involved in promoting important malignant features, such as the acquisition of a cancer stem-like and metastatic phenotype. Based on previous studies showing that KRAS activates nuclear factor kappa-B (NF-κB) through inhibitor of nuclear factor kappa-B kinase β (IKKβ) to promote lung tumourigenesis, we hypothesized that inhibition of IKKβ would reduce stemness, migration and invasion of KRAS-mutant human lung cancer cells. We show that KRAS-driven lung tumoursphere-derived cells exhibit stemness features and increased IKKβ kinase activity. IKKβ targeting by different approaches reduces the expression of stemness-associated genes, tumoursphere formation, and self-renewal, and preferentially impairs the proliferation of KRAS-driven lung tumoursphere-derived cells. Moreover, we show that IKKβ targeting reduces tumour cell migration and invasion, potentially by regulating both expression and activity of matrix metalloproteinase 2 (MMP2). In conclusion, our results indicate that IKKβ is an important mediator of KRAS-induced stemness and invasive features in lung cancer, and, therefore, might constitute a promising strategy to lower recurrence rates, reduce metastatic dissemination, and improve survival of lung cancer patients with KRAS-driven disease.
journal_name
Int J Mol Scijournal_title
International journal of molecular sciencesauthors
Rodrigues FS,Miranda VS,Carneiro-Lobo TC,Scalabrini LC,Kruspig B,Levantini E,Murphy DJ,Bassères DSdoi
10.3390/ijms21165806subject
Has Abstractpub_date
2020-08-13 00:00:00issue
16issn
1422-0067pii
ijms21165806journal_volume
21pub_type
杂志文章abstract：BACKGROUND:It is well known that diabetes mellitus impairs immunity and therefore is an independent risk factor for tuberculosis. However, the influence of associated metabolic factors, such as hypertension, dyslipidemia and gout has yet to be confirmed. This study aimed to investigate whether the strong association be...
journal_title：International journal of molecular sciences
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abstract：:The phototoxic effect of hypericin can be utilized for Photodynamic Therapy (PDT) of cancer. After intravenous application and systemic distribution of the drug in the patient's body, the tumor site is exposed to light. Subsequently, toxic reactive oxygen species (ROS) are generated, inducing tumor cell death. To prev...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms18071388
更新日期：2017-06-29 00:00:00
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journal_title：International journal of molecular sciences
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journal_title：International journal of molecular sciences
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abstract：:Clofazimine (CLZ) is an effective antibiotic used against a wide spectrum of Gram-positive bacteria and leprosy. One of its main drawbacks is its poor solubility in water. Silica based materials are used as drug delivery carriers that can increase the solubility of different hydrophobic drugs. Here, we studied how the...
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journal_title：International journal of molecular sciences
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abstract：:The aim of this PRISMA review was to assess whether the CMI and Actifit scaffolds, when used in clinical practice, improve clinical outcomes and demonstrate the ideal biological and biomechanical properties of scaffolds: being chondroprotective, porous, resorbable, able to mature and promote regeneration of tissue. Th...
journal_title：International journal of molecular sciences
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journal_title：International journal of molecular sciences
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更新日期：2019-10-30 00:00:00
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更新日期：2018-07-17 00:00:00
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journal_title：International journal of molecular sciences
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journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms20051133
更新日期：2019-03-06 00:00:00
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doi：10.3390/ijms17060971
更新日期：2016-06-20 00:00:00
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journal_title：International journal of molecular sciences
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doi：10.3390/ijms18102176
更新日期：2017-10-18 00:00:00
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journal_title：International journal of molecular sciences
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journal_title：International journal of molecular sciences
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journal_title：International journal of molecular sciences
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journal_title：International journal of molecular sciences
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journal_title：International journal of molecular sciences
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journal_title：International journal of molecular sciences
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abstract：:Serum amyloid A (SAA) promotes endothelial inflammation and dysfunction that is associated with cardiovascular disease and renal pathologies. SAA is an apoprotein for high-density lipoprotein (HDL) and its sequestration to HDL diminishes SAA bioactivity. Herein we investigated the effect of co-supplementing HDL on SAA...
journal_title：International journal of molecular sciences
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abstract：:Mast cells (MC) are resident tissue cells found primarily at the interphase between tissues and the environment. These evolutionary old cells store large amounts of proteases within cytoplasmic granules, and one of the most abundant of these proteases is tryptase. To look deeper into the question of their in vivo targ...
journal_title：International journal of molecular sciences
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abstract：:Tanshinone IIA (Tan-IIA) is an extract from the widely used traditional Chinese medicine (TCM) Danshen (Salvia miltiorrhiza), and has been found to attenuate the proliferation of bladder cancer (BCa) cells (The IC50 were: 5637, 2.6 μg/mL; BFTC, 2 μg/mL; T24, 2.7 μg/mL, respectively.). However, the mechanism of the eff...
journal_title：International journal of molecular sciences
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abstract：:Wounding is a serious environmental stress in plants. Oxylipins such as jasmonic acid play an important role in defense against wounding. Mechanisms to adapt to wounding have been investigated in vascular plants; however, those mechanisms in nonvascular plants remain elusive. To examine the response to wounding in Phy...
journal_title：International journal of molecular sciences
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doi：10.3390/ijms21041417
更新日期：2020-02-19 00:00:00
