Extracellular signal-regulated kinase 8 (ERK8), also known as mitogen-activated protein kinase 15 (MAPK15), is the most recently identified protein kinase of the ERK family members and yet the least has been studied so far. Here, we report that ERK8 is highly expressed in several human lung cancer cell lines and is positively correlated with their sensitivities to the anti-cancer drug arsenic trioxide (As2O3). As2O3 at physiologically relevant concentrations (5-20 μM) potently stimulates the phosphorylation of ERK8 at Thr175 and Tyr177 within the TEY motif in the kinase domain, leading to its activation. Interestingly, activated ERK8 interacts and directly phosphorylates IkappaBalpha (IκBα) at Ser32 and Ser36, resulting in IκBα degradation. This in turn promotes nuclear factor-kappaB (NF-κB) p65 nuclear translocation and chromatin-binding, as well as the subsequent induction and activation of proteins involved in apoptosis. We also show that stable short-hairpin RNA-specific knockdown of endogenous ERK8 or inhibition of NF-κB activity by NF-κB inhibitor in high ERK8 expressing lung cancer H1299 cells blunted the As2O3-induced NF-κB activation and cytotoxicity towards these cells, indicating the critical role of ERK8 and NF-κB in mediating the As2O3 effects. Taken together, our findings suggest for the first time a regulatory paradigm of NF-κB activation by ERK8 upon As2O3 treatment in human lung cancer cells; and implicate a potential therapeutic advantage of As2O3 that might gain more selective killing of cancer cells with high ERK8 expression.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5564756 | PMC |
http://dx.doi.org/10.18632/oncotarget.17100 | DOI Listing |
J Med Imaging Radiat Oncol
December 2024
Department of Radiology, Grampians Health, Ballarat Central, Victoria, Australia.
Background: CT-guided percutaneous transthoracic needle biopsy is the primary method for diagnosing lung lesions. Widely accepted validated risk prediction models are yet to be developed. A recently published study conducted at Grampians Health Services (GHS) developed two risk prediction models for predicting pneumothorax and intercostal catheter (ICC) insertion.
View Article and Find Full Text PDFPLoS One
December 2024
Department of Water Resources, Climatology and Environmental Management, University of Warmia and Mazury in Olsztyn, Olsztyn, Poland.
Introduction: Lung cancer, one of the leading causes of death due to neoplasms, requires prompt diagnosis and immediate treatment. The COVID-19 pandemic affected healthcare systems worldwide, having adverse effects on all aspects, particularly on the fate of patients with suspected neoplastic diseases. Limited access to healthcare, disruptions in regular operations (reassigning roles to some wards), postponed hospital admissions, prolonged diagnostic processes, and other factors have collectively led to the phenomenon known as COVID-19 debt.
View Article and Find Full Text PDFElife
December 2024
Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.
Chemotherapy is widely used to treat lung adenocarcinoma (LUAD) patients comprehensively. Considering the limitations of chemotherapy due to drug resistance and other issues, it is crucial to explore the impact of chemotherapy and immunotherapy on these aspects. In this study, tumor samples from nine LUAD patients, of which four only received surgery and five received neoadjuvant chemotherapy, were subjected to scRNA-seq analysis.
View Article and Find Full Text PDFJAMA Netw Open
December 2024
Department of Radiation Oncology, Wake Forest University School of Medicine, Winston-Salem, North Carolina.
Importance: Radiotherapy (RT) plan quality is an established predictive factor associated with cancer recurrence and survival outcomes. The addition of radiologists to the peer review (PR) process may increase RT plan quality.
Objective: To determine the rate of changes to the RT plan with and without radiology involvement in PR of radiation targets.
Discov Oncol
December 2024
Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, 310022, Zhejiang, China.
Antibody-drug conjugates (ADCs) represent a novel class of targeted anti-tumor medications that utilize the covalent linkage between monoclonal antibodies and cytotoxic agents. This unique mechanism combines the cytotoxic potency of drugs with the targeting specificity conferred by antigen recognition. However, it is essential to recognize that many ADCs still face challenges related to off-target toxicity akin to cytotoxic payloads, as well as targeted toxicity and other potential life-threatening adverse effects, such as treatment-induced interstitial lung injury.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!