AMPK/FOXO3a Pathway Increases Activity and/or Expression of ATM, DNA-PKcs, Src, EGFR, PDK1, and SOD2 and Induces Radioresistance under Nutrient Starvation

نویسندگان

چکیده

Most solid tumors contain hypoxic and nutrient-deprived microenvironments. The cancer cells in these microenvironments have been reported to exhibit radioresistance. We previously that nutrient starvation increases the expression and/or activity of ATM DNA-PKcs, which are involved repair DNA double-strand breaks induced by ionizing radiation. In present study, elucidate molecular mechanisms underlying phenomena, we investigated roles AMPK FOXO3a, play key cellular response starvation. Nutrient increased clonogenic cell survival after irradiation AMPKα, ATM, Src, EGFR, PDK1, SOD2 MDA-MB-231 cells. Knockdown AMPKα using siRNA suppressed under FOXO3a decreased incidence apoptosis 8 Gy irradiation. appear be molecules induce radioresistance may serve as targets for radiosensitization.

برای دانلود باید عضویت طلایی داشته باشید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

ATM induces radioresistance of non-small cell lung cancer A549 cells by downregulation of MDMX

Background: Tumor radioresistance leads to a reduction in the efficiency of radiation therapy. It is very important to explore the cellular mechanisms leading to radioresistance and to find potential therapeutic targets, which might improve the efficacy of radiation therapy. This study was to investigate the role of ataxia-telangiectasia mutated (ATM) and murine double minute X (MDMX) in radior...

متن کامل

antioxidant and antimicrobial activity of allium jesdianum extract

چکیده بررسی فعالیت ضد اکسیدانی و ضدمیکروبی عصاره گیاه بن سرخ (allium jesdianum) به کوشش: زهرا مقیمی هدف از این تحقیق بررسی میزان ترکیبات فنولی کل، ترکیبات فلاوونوئیدی کل، فعالیت ضداکسیدانی و ضدمیکروبی عصاره ی گیاه تازه و خشک بن سرخ بود. استخراج عصاره به روش های غوطه وری، استفاده از همزن مغناطیسی، دستگاه مایکروویو، امواج فراصوت و گرمادهی مقاومتی و با استفاده از متانول، اتانول و آب به عنوا...

DNA Damage and Cellular Stress Responses Threonine 2609 Phosphorylation of the DNA-Dependent Protein Kinase Is aCritical Prerequisite for Epidermal Growth Factor Receptor–Mediated Radiation Resistance

The EGF receptor (EGFR) contributes to tumor radioresistance, in part, through interactions with the catalytic subunit of DNA-dependent protein kinase (DNA-PKc), a key enzyme in the nonhomologous end joining DNA repair pathway. We previously showed that EGFR-DNA-PKcs interactions are significantly compromised in the context of activating mutations in EGFR in non–small cell lung carcinoma (NSCLC...

متن کامل

Distinct roles of ATR and DNA-PKcs in triggering DNA damage responses in ATM-deficient cells.

The cellular response to DNA double-strand breaks involves direct activation of ataxia telangiectasia mutated (ATM) and indirect activation of ataxia telangiectasia and Rad3 related (ATR) in an ATM/Mre11/cell-cycle-dependent manner. Here, we report that the crucial checkpoint signalling proteins-p53, structural maintainance of chromosomes 1 (SMC1), p53 binding protein 1 (53BP1), checkpoint kina...

متن کامل

Regulation of pairing between broken DNA-containing chromatin regions by Ku80, DNA-PKcs, ATM, and 53BP1

Chromosome rearrangement is clinically and physiologically important because it can produce oncogenic fusion genes. Chromosome rearrangement requires DNA double-strand breaks (DSBs) at two genomic locations and misrejoining between the DSBs. Before DSB misrejoining, two DSB-containing chromatin regions move and pair with each other; however, the molecular mechanism underlying this process is la...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

ژورنال

عنوان ژورنال: International Journal of Molecular Sciences

سال: 2023

ISSN: ['1661-6596', '1422-0067']

DOI: https://doi.org/10.3390/ijms241612828