eIF2{alpha} Phosphorylation Mediates IL24-Induced Apoptosis through Inhibition of Translation

IL24 is an immunomodulatory cytokine that also displays broad cancer-specific suppressor effects. The tumor-suppressor activities of IL24 include inhibition of angiogenesis, sensitization to chemotherapy, and cancer-specific apoptosis. Supra-physiologic activation and/or overexpression of translation initiation factors are implicated in the initiation and progression of cancer animal models as well as a subset of human cancers. Activation and/or overexpression of translation initiation factors correlate with aggressiveness of cancer and poor prognosis. Two rate-limiting translation initiation complexes, the ternary complex and the eIF4F complex, are regulated by eIF2α and 4E-BP1 phosphorylation, respectively. The work reported here provides direct evidence that IL24 induces inhibition of translation initiation leading to apoptosis in squamous cell carcinoma. A dominant constitutively active mutant of eIF2α, which is resistant to phosphorylation, was used to determine the involvement of eIF2α in IL24-induced apoptosis. Treatment with IL24 resulted in inhibition of protein synthesis, expression of downstream biomarkers of ternary complex depletion such as CHOP, and induction of apoptosis in cancer cells. The constitutively active nonphosphorylatable mutant of eIF2α, eIF2α-S51A, reversed both the IL24-mediated translational block and IL24-induced apoptosis. Intriguingly, IL24 treatment also caused hypophosphorylation of 4E-BP1, which binds to eIF4E ...
Source: Molecular Cancer Research - Category: Cancer & Oncology Authors: Tags: Signal Transduction Source Type: research

Related Links:

Conclusion Anlotinib effectively controlled the growth of NSCLC and improved TAO related symptoms. Anlotinib maybe normalize disordered growth of blood vessels through the VEGF signaling pathway, rather than simply inhibiting angiogenesis. 
 DOI: 10.3779/j.issn.1009-3419.2020.01.10
Source: Chinese Journal of Lung Cancer - Category: Cancer & Oncology Source Type: research
Immune checkpoint inhibitors that block the programmed death 1/programmed death ligand 1 pathways are widely used to treat advanced lung cancers. There are seldom cases of histologic transformation reported after treatment with immunotherapy. Here, we report the case of a 69 ‐year‐old man with stage IV lung squamous cell carcinoma. He received pembrolizumab monotherapy and had a partial response. After 22 cycles of pembrolizumab, chest computed tomography (CT) showed a left hilar tumor, bilateral pleural effusion and lymphadenopathy. The cytology of pleural effusion and bronchoscopic biopsy of an intraluminal lesion re...
Source: Thoracic Cancer - Category: Cancer & Oncology Authors: Tags: CASE REPORT Source Type: research
BackgroundThis retrospective study compared the efficacy and side effect profile between postoperative adjuvant radiotherapy and chemoradiotherapy in stage II or stage III thoracic esophageal squamous cell carcinoma (TESCC) patients who underwent curative (R0) esophagectomy.MethodsA total of 272 TESCC patients who underwent radical esophagectomy from 2007 to 2016 were included in this retrospective analysis. All cases were pathologically confirmed with stage II or III disease and 148 patients received postoperative chemoradiotherapy (CRT), while the remaining 124 patients received postoperative radiotherapy (RT) alone.Resu...
Source: Thoracic Cancer - Category: Cancer & Oncology Authors: Tags: ORIGINAL ARTICLE Source Type: research
ConclusionsPCE as IC was feasible, with promising efficacy and no effect on compliance with subsequent CRT in unresectable LA ‐SCCHN.
Source: Cancer Medicine - Category: Cancer & Oncology Authors: Tags: ORIGINAL RESEARCH Source Type: research
CONCLUSION: Pretreatment texture parameters are associated with survival time, and the combination of post volume performed better in survival models. PMID: 31903981 [PubMed - as supplied by publisher]
Source: Cancer Biomarkers - Category: Cancer & Oncology Tags: Cancer Biomark Source Type: research
SummaryCutaneous squamous cell carcinoma (cSCC) accounts for approximately 20% of all skin cancers. Its rising incidence represents a major public health concern. The majority of cSCC are curable by surgical resection. Although less than 5% of cSCC patients develop metastases or local recurrence after complete excision, advanced cSCC is difficult to treat. Until recently, no standard therapeutic regimen for advanced cSCC exists. Traditional therapies include chemotherapy and EGFR-targeted therapy, but their clinical benefit remains modest and has been demonstrated mostly in retrospective studies. On the contrary, PD-1 inhi...
Source: Memo - Magazine of European Medical Oncology - Category: Cancer & Oncology Source Type: research
In this study, we investigated a panel of naturally occurring PNPs to identify more efficient enzymes that may be suitable for metabolizing F-araA as part of experimental cancer therapy. We show thatTrichomonas vaginalis PNP (TvPNP) cleaves F-araA with a catalytic efficiency 25-fold greater than the prototypicE. coli enzyme. Cellular extracts from human glioma cells (D54) transduced with lentivirus stably expressingTvPNP (D54/TvPNP) were found to cleave F-araA at a rate similar to extracts from D54 cells expressingEcPNP, although much less enzyme was expressed per cell in theTvPNP transduced condition. As a test of safety ...
Source: Cancer Chemotherapy and Pharmacology - Category: Cancer & Oncology Source Type: research
Authors: Lee MC, Chen YK, Hsu YJ, Lin BR Abstract Niclosamide is an FDA‑approved anthelmintic drug, and may elicit antineoplastic effects through direct STAT3 inhibition, which has been revealed in numerous human cancer cells. Chemotherapy is the standard treatment for advanced esophageal cancers, but also causes severe systemic side effects. The present study represents the first study evaluating the anticancer efficacy of niclosamide in esophageal cancers. Through western blot assay, it was demonstrated that niclosamide suppressed the STAT3 signaling pathway in esophageal adenocarcinoma cells (BE3) and esophage...
Source: Oncology Reports - Category: Cancer & Oncology Tags: Oncol Rep Source Type: research
Conclusions: Sebaceous carcinoma currently has few effective adjuvant treatment options. The expression of PD-1, PD-L1, and PD-L2 on infiltrating immune cells and PD-L2 on tumor cells restrains T-cells from full activation and proliferation, therefore limiting the antitumor effect of T-cells, tipping the balance toward unopposed tumor progression. Consequently, PD-1 or PD-L1 inhibitors may have a role in sebaceous carcinoma treatment. Given the prevalence of PD-L2 expression in sebaceous carcinoma and the lack of PD-L2 blockade therapy available, PD-1 blockade may provide benefit over PD-L1 inhibitors. PD-1 blockade in c...
Source: Ophthalmic Plastic and Reconstructive Surgery - Category: Opthalmology Tags: Original Investigations Source Type: research
Half of patients newly diagnosed with esophageal squamous cell cancer (ESCC) have metastatic disease (mESCC) and therefore a poor prognosis. Furthermore, half of patients with initial loco-regional disease present disease recurrence after surgery and/or chemoradiation. In mESCC, the recommended first-line treatment combines 5-fluorouracil and cisplatin, although this has not been validated by a phase III trial. Patients with disease progression or recurrence after platinum-based chemotherapy and good performance status probably benefit from second-line chemotherapy.
Source: Digestive and Liver Disease - Category: Gastroenterology Authors: Tags: Progress Report Source Type: research
More News: Cancer | Cancer & Oncology | Carcinoma | Chemotherapy | Genetics | Skin Cancer | Squamous Cell Carcinoma