Proteome-wide screening for the analysis of protein targeting of Chlamydia pneumoniae in endoplasmic reticulum of host cells and their possible implication in lung cancer development

AbstractCisplatin is a frontline cancer therapeutic, but intrinsic or acquired resistance is common. We previously showed that cisplatin sensitivity can be achieved by inactivation of ASNA-1/TRC40 in mammalian cancer cells and in Caenorhabditis elegans. ASNA-1 has two more conserved functions: in promoting tail-anchored protein (TAP) targeting to the endoplasmic reticulum membrane and in promoting insulin secretion. However, the relation between its different functions has remained unknown. Here, we show that ASNA-1 exists in two redox states that promote TAP-targeting and insulin secretion separately. The reduced state is the one required for cisplatin resistance: an ASNA-1 point mutant, in which the protein preferentially was found in the oxidized state, was sensitive to cisplatin and defective for TAP targeting but had no insulin secretion defect. The same was true for mutants in wrb-1, which we identify as the C. elegans homolog of WRB, the ASNA1/TRC40 receptor. Finally, we uncover a previously unknown action of cisplatin induced reactive oxygen species: cisplatin induced ROS drives ASNA-1 into the oxidized form, and selectively prevents an ASNA-1-dependent TAP substrate from reaching the endoplasmic reticulum. Our work suggests that ASNA-1 acts as a redox-sensitive target for cisplatin cytotoxicity and that cisplatin resistance is likely mediated by ASNA-1-dependent TAP substrates. Treatments that promote an oxidizing tumor environment should be explored as possible means to combat cisplatin resistance.

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Comprehensive Perspective for Lung Cancer Characterisation Based on AI Solutions Using CT Images

Journal of Clinical Medicine ◽

10.3390/jcm10010118 ◽

2020 ◽

Vol 10 (1) ◽

pp. 118

Author(s):

Tania Pereira ◽

Cláudia Freitas ◽

José Luis Costa ◽

Joana Morgado ◽

Francisco Silva ◽

...

Keyword(s):

Lung Cancer ◽

Targeted Therapies ◽

Treatment Plan ◽

Personalised Medicine ◽

Growth Factor Receptor ◽

Accurate Diagnosis ◽

Cancer Development ◽

Thoracic Computed Tomography ◽

Plan Selection ◽

Ct Image Analysis

Lung cancer is still the leading cause of cancer death in the world. For this reason, novel approaches for early and more accurate diagnosis are needed. Computer-aided decision (CAD) can be an interesting option for a noninvasive tumour characterisation based on thoracic computed tomography (CT) image analysis. Until now, radiomics have been focused on tumour features analysis, and have not considered the information on other lung structures that can have relevant features for tumour genotype classification, especially for epidermal growth factor receptor (EGFR), which is the mutation with the most successful targeted therapies. With this perspective paper, we aim to explore a comprehensive analysis of the need to combine the information from tumours with other lung structures for the next generation of CADs, which could create a high impact on targeted therapies and personalised medicine. The forthcoming artificial intelligence (AI)-based approaches for lung cancer assessment should be able to make a holistic analysis, capturing information from pathological processes involved in cancer development. The powerful and interpretable AI models allow us to identify novel biomarkers of cancer development, contributing to new insights about the pathological processes, and making a more accurate diagnosis to help in the treatment plan selection.

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ZEB1 induces non-small cell lung cancer development by targeting microRNA-320a to increase the expression of RAD51AP1

Experimental Cell Research ◽

10.1016/j.yexcr.2021.112687 ◽

2021 ◽

pp. 112687

Author(s):

Huifeng Wang ◽

Hui Dong ◽

Lijiao Qiao ◽

Yuanyuan Wu ◽

Bo Wu ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Small Cell ◽

Cancer Development ◽

Small Cell Lung

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Lung cancer development in patients with connective tissue disease–related interstitial lung disease

Medicine ◽

10.1097/md.0000000000005716 ◽

2016 ◽

Vol 95 (50) ◽

pp. e5716 ◽

Cited By ~ 6

Author(s):

Yasunori Enomoto ◽

Naoki Inui ◽

Katsuhiro Yoshimura ◽

Koji Nishimoto ◽

Kazutaka Mori ◽

...

Keyword(s):

Lung Cancer ◽

Interstitial Lung Disease ◽

Connective Tissue ◽

Lung Disease ◽

Connective Tissue Disease ◽

Cancer Development

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Differential Impacts of Insulin-Like Growth Factor-Binding Protein-3 (IGFBP-3) in Epithelial IGF-Induced Lung Cancer Development

Endocrinology ◽

10.1210/en.2010-0693 ◽

2011 ◽

Vol 152 (6) ◽

pp. 2164-2173 ◽

Cited By ~ 13

Author(s):

Woo-Young Kim ◽

Mi-Jung Kim ◽

Hojin Moon ◽

Ping Yuan ◽

Jin-Soo Kim ◽

...

Keyword(s):

Lung Cancer ◽

Lung Tumor ◽

Binding Protein ◽

Cancer Development ◽

Lung Carcinogenesis ◽

Tobacco Carcinogen ◽

Igf I ◽

The Impact ◽

Igfbp 3

The IGF axis has been implicated in the risk of various cancers. We previously reported a potential role of tissue-derived IGF in lung tumor formation and progression. However, the role of IGF-binding protein (IGFBP)-3, a major IGFBP, on the activity of tissue-driven IGF in lung cancer development is largely unknown. Here, we show that IGF-I, but not IGF-II, protein levels in non-small-cell lung cancer (NSCLC) were significantly higher than those in normal and hyperplastic bronchial epithelium. We found that IGF-I and IGFBP-3 levels in NSCLC tissue specimens were significantly correlated with phosphorylated IGF-IR (pIGF-IR) expression. We investigated the impact of IGFBP-3 expression on the activity of tissue-driven IGF-I in lung cancer development using mice carrying lung-specific human IGF-I transgene (Tg), a germline-null mutation of IGFBP-3, or both. Compared with wild-type (BP3+/+) mice, mice carrying heterozygous (BP3+/−) or homozygous (BP3−/−) deletion of IGFBP-3 alleles exhibited decreases in circulating IGFBP-3 and IGF-I. Unexpectedly, IGFTg mice with 50% of physiological IGFBP-3 (BP3+/−; IGFTg) showed higher levels of pIGF-IR/IR and a greater degree of spontaneous or tobacco carcinogen [4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone]-induced lung tumor development and progression than did the IGFTg mice with normal (BP3+/+;IGFTg) or homozygous deletion of IGFBP-3 (BP3−/−; IGFTg). These data show that IGF-I is overexpressed in NSCLC, leading to activation of IGF-IR, and that IGFBP-3, depending on its expression level, either inhibits or potentiates IGF-I actions in lung carcinogenesis.

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Ciprofloxacin Enhances TRAIL-Induced Apoptosis in Lung Cancer Cells by Upregulating the Expression and Protein Stability of Death Receptors through CHOP Expression

International Journal of Molecular Sciences ◽

10.3390/ijms19103187 ◽

2018 ◽

Vol 19 (10) ◽

pp. 3187 ◽

Cited By ~ 8

Author(s):

Eun Lim ◽

Yu Yoon ◽

Jeonghoon Heo ◽

Tae Lee ◽

Young-Ho Kim

Keyword(s):

Lung Cancer ◽

Protein Stability ◽

Cancer Cells ◽

Death Receptor ◽

Proteolytic Processing ◽

Receptor Expression ◽

Host Cells ◽

Lung Cancer Cells ◽

Regulation Of Transcription ◽

Induced Apoptosis

Ciprofloxacin (CIP) is a potent antimicrobial agent with multiple effects on host cells and tissues. Previous studies have highlighted their proapoptotic effect on human cancer cells. The current study showed that subtoxic doses of CIP effectively sensitized multiple cancer cells to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis. Although TRAIL alone mediated the partial proteolytic processing of procaspase-3 in lung cancer cells, co-treatment with CIP and TRAIL efficiently restored the complete activation of caspases. We found that treatment of lung cancer with CIP significantly upregulated the expression and protein stability of death receptor (DR) 5. These effects were mediated through the regulation of transcription factor CCAT enhancer-binding protein homologous protein (CHOP) since the silencing of these signaling molecules abrogated the effect of CIP. Taken together, these results indicated that the upregulation of death receptor expression and protein stability by CIP contributed to the restoration of TRAIL-sensitivity in lung cancer cells.

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