Calpain-2 Enhances Non-Small Cell Lung Cancer Progression and Chemoresistance to Paclitaxel via EGFR-pAKT Pathway

Xu, Fan; Gu, Jie; Chen, Lu; Mao, Wei; Wang, Lin; Zhu, Qinqing; Liu, Zhonghe; Chu, Yiwei; Liu, Ronghua

doi:10.7150/ijbs.28834

Cited by 28 publications

(17 citation statements)

References 37 publications

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“…As a consequence of the intramembranous cleavage of HO-1 by SPP, a t-HO-1 form was generated that underwent nuclear translocation [ 88 ]. Other potential enzymes able to cleave HO-1 as cathepsin B [ 89 , 90 ] and calpain-2 [ 91 ] were shown to be overexpressed in lung cancer, but their participation in HO-1 truncation remains to be demonstrated. Once inside the nucleus, t-HO-1 was able to induce cell proliferation, migration and invasion, independently of its enzymatic activity.…”

Section: Nuclear Ho-1 In Cancermentioning

confidence: 99%

Nuclear Localization of Heme Oxygenase-1 in Pathophysiological Conditions: Does It Explain the Dual Role in Cancer?

Mascaró

Alonso

et al. 2021

Antioxidants

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Heme Oxygenase-1 (HO-1) is a type II detoxifying enzyme that catalyzes the rate-limiting step in heme degradation leading to the formation of equimolar quantities of carbon monoxide (CO), free iron and biliverdin. HO-1 was originally shown to localize at the smooth endoplasmic reticulum membrane (sER), although increasing evidence demonstrates that the protein translocates to other subcellular compartments including the nucleus. The nuclear translocation occurs after proteolytic cleavage by proteases including signal peptide peptidase and some cysteine proteases. In addition, nuclear translocation has been demonstrated to be involved in several cellular processes leading to cancer progression, including induction of resistance to therapy and enhanced metastatic activity. In this review, we focus on nuclear HO-1 implication in pathophysiological conditions with special emphasis on malignant processes. We provide a brief background on the current understanding of the mechanisms underlying how HO-1 leaves the sER membrane and migrates to the nucleus, the circumstances under which it does so and, maybe the most important and unknown aspect, what the function of HO-1 in the nucleus is.

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Section: Nuclear Ho-1 In Cancermentioning

confidence: 99%

Nuclear Localization of Heme Oxygenase-1 in Pathophysiological Conditions: Does It Explain the Dual Role in Cancer?

Mascaró

Alonso

et al. 2021

Antioxidants

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“…For the analysis of CXCR4 expression on the response to PTX, at 24 hours after transfection, cells were treated with 20nM PTX for another 48 hours. Apoptosis analysis was performed using Annexin V-FITC/PI Apoptosis Detection Kit (YEASEN, Shanghai, CN) and cells were detected with flow cytometry on a FACScan (BD Biosciences, NJ, USA) in the corresponding procedures as described previously 21 .…”

Section: Cck-8 Assay Transwell Assay and Cell Apoptosis Analysismentioning

confidence: 99%

High CXCR4 Expression Predicts a Poor Prognosis in Resected Lung Adenosquamous Carcinoma

Zhu¹,

Luo²,

Gu³

et al. 2020

J. Cancer

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Background: Primary adenosquamous carcinoma (ASC) is a rare malignant tumor in the lung and its biological behavior has not yet been thoroughly described. In this study, we aimed to explore the clinical and biological role of CXCR4 in patients with resected lung ASC. Methods: We retrospectively reviewed the clinical records of patients with histologically confirmed lung ASC who underwent surgical resection with systematic lymph node dissection. Immunohistochemical staining was performed to detect the expression of CXCR4 in tumor tissues. The correlation between CXCR4 expression and clinicopathological characteristics were evaluated. The association between CXCR4 expression and patients' prognosis was analyzed by Kaplan-Meier and Cox regression. Moreover, we performed in vitro studies including CCK8, transwell and cell apoptosis to explore the potential role of CXCR4 in lung ASC. Results:A total of 78 patients with resected lung ASC were reviewed. Seventy (89.7%) patient tumors expressed CXCR4, with high level of CXCR4 expression observed in 45 (57.7%) cases. In vitro, CXCR4 conferred no difference in proliferative capacity but increased invasive potential, enhanced chemoresistance and inhibited apoptosis of lung ASC. Clinically, high CXCR4 expression was significantly associated with solid ASC, lymph node metastasis and advanced TNM stage. Patients with high CXCR4 expression and solid ASC had decreased disease-free survival and overall survival. Conclusions: CXCR4 was commonly expressed in lung ASC tumors. High CXCR4 expression might be a novel marker in predicting a poor prognosis in resected lung ASC and might serve as a potential therapeutic target.

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“…International Publisher used as anticancer drug for a series of malignancies, including breast, endometrial, liver, bile duct and esophageal cancers [5][6][7][8]. Patients generally show a favorable initial response to PTX, however, the efficacy of PTX is frequently restricted by the lack of tumor specificity.…”

Section: Ivyspringmentioning

confidence: 99%

Molecular Mechanism for Selective Cytotoxicity towards Cancer Cells of Diselenide-Containing Paclitaxel Nanoparticles

Zhang

et al. 2019

Int. J. Biol. Sci.

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Diselenide-containing paclitaxel nanoparticles (SePTX NPs) indicated selectivity of cytotoxicity between cancerous and normal cells in our previous work. Herein, the mechanism is revealed by molecular biology in detail. Cancer cells and normal cells were treated with the SePTX NPs and cell proliferation was measured using 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide (MTT) assay and cell morphology. Measurement of reactive oxygen species (ROS) levels and biochemical parameters were employed to monitor oxidative stress of the cells. JC-1 assay was used to detect the mitochondrial dysfunction of the cells. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) analysis was used to detect apoptosis of the cells. Immunofluorescence analysis and western blotting were employed to monitor changes in signaling pathway-related proteins. Compared with PTX, SePTX NPs has a good selectivity to cancer cells and can obviously induce the proliferation damage of cancer cells, but has no significant toxicity to normal cells, indicating that SePTX NPs has a specific killing effect on cancer cells. The results of mechanism research show that SePTX NPs can successfully inhibit the depolymerization of microtubules and induce cell cycle arrest, which is related to the upregulation of p53 and CyclinB1. Simultaneously, SePTX NPs can successfully induce oxidative stress, cause mitochondrial dysfunction, resulting in mitochondrial pathway-mediated apoptosis, which is related to the upregulation of autophagy-related protein LC3-II. On the other hand, lewis lung cancer C57BL/6 mice were used to evaluate the anti-tumor effects of SePTX NPs in vivo. Our data show that SePTX NPs exhibited high inhibiting efficiency against the growth of tumors and were able to reduce the side effects. Collectively, these data indicate that the high antitumor effect and selective cytotoxicities of SePTX NPs is promising in future cancer therapy.

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Calpain-2 Enhances Non-Small Cell Lung Cancer Progression and Chemoresistance to Paclitaxel via EGFR-pAKT Pathway

Cited by 28 publications

References 37 publications

Nuclear Localization of Heme Oxygenase-1 in Pathophysiological Conditions: Does It Explain the Dual Role in Cancer?

Nuclear Localization of Heme Oxygenase-1 in Pathophysiological Conditions: Does It Explain the Dual Role in Cancer?

High CXCR4 Expression Predicts a Poor Prognosis in Resected Lung Adenosquamous Carcinoma

Molecular Mechanism for Selective Cytotoxicity towards Cancer Cells of Diselenide-Containing Paclitaxel Nanoparticles

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