The inhibition of the central growth regulatory kinase TOR, which participates in two complexes, TORC1 and TORC2, has been a focus of metabolic and cancer studies for many years. Most studies have dealt with TORC1, the canonical target of rapamycin, and the role of this complex in autophagy, protein synthesis, and cell growth control. Recent work on TORC2 in budding and fission yeast species points to a conserved role of this lesser-known TOR complex in the survival of DNA damage. In budding yeast, TORC2 controls lipid biosynthesis and actin cytoskeleton through downstream AGC kinases, which are now, surprisingly, implicated in the survival of oxidative DNA damage. Preliminary data from mTORC2 modulation in cancer cells suggest that an extension to human chemotherapy is worth exploring.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4154128 | PMC |
| http://dx.doi.org/10.15252/emmm.201403959 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
HSF1 at the crossroads of chemoresistance: from current insights to future horizons in cell death mechanisms.
Front Cell Dev Biol
January 2025
Department of Cell and Cancer Biology, College of Medicine and Life Sciences, The University of Toledo, Toledo, OH, United States.
Heat Shock Factor 1 (HSF1) is a major transcriptional factor regulating the heat shock response and has become a potential target for overcoming cancer chemoresistance. This review comprehensively examines HSF1's role in chemoresistance and its potential as a therapeutic target in cancer. We explore the complex, intricate mechanism that regulates the activation of HSF1, HSF1's function in promoting resistance to chemotherapy, and the strategies used to manipulate HSF1 for therapeutic benefit.
View Article and Find Full Text PDFA Novel Homozygous Mutation Causes Ovarian Dysgenesis and Primary Amenorrhea.
J Endocr Soc
January 2025
Division of Pediatric Endocrinology, Hadassah Medical Center, Jerusalem 91240, Israel.
Context: Despite a growing number of studies, the genetic etiology in many cases of ovarian dysgenesis is incompletely understood.
Objectives: This work aimed to study the genetic etiology causing absence of spontaneous pubertal development, hypergonadotropic hypogonadism, and primary amenorrhea in 2 sisters.
Methods: Whole-exome sequencing was performed on DNA extracted from peripheral lymphocytes of 2 Palestinian sisters born to consanguineous parents.
Polydatin enhances oxaliplatin-induced cell death by activating NOX5-ROS-mediated DNA damage and ER stress in colon cancer cells.
Front Pharmacol
January 2025
The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
Background: Polydatin (3,4',5-trihydroxy-3-β-d-glucopyranoside, PD) is known for its antioxidant and anti-inflammatory properties. Oxaliplatin (OXA)-based chemotherapy is the first-line treatment for metastatic and recurrent colorectal cancer (CRC). However, the lack of selectivity for normal cells often results in side effects.
View Article and Find Full Text PDFAntioxidant therapy for infertile couples: a comprehensive review of the current status and consideration of future prospects.
Front Endocrinol (Lausanne)
January 2025
Department of Obstetrics and Gynaecology, Assiut University, Assiut, Egypt.
Oxidative stress (OS) is established as a key factor in the etiology of both male and female infertility, arising from an imbalance between reactive oxygen species (ROS) production and the endogenous antioxidant (AOX) defenses. In men, OS adversely affects sperm function by inducing DNA damage, reducing motility, significantly impairing sperm vitality through plasma membrane peroxidation and loss of membrane integrity, and ultimately compromising overall sperm quality. In women, OS is implicated in various reproductive disorders, including polycystic ovary syndrome, endometriosis, and premature ovarian failure, leading to diminished oocyte quality, disrupted folliculogenesis, and poorer reproductive outcomes.
View Article and Find Full Text PDFMitochondrial DNA oxidation and content in different metabolic phenotypes of women with polycystic ovary syndrome.
Front Endocrinol (Lausanne)
January 2025
Facultad de Farmacia y Bioquímica, Departamento de Microbiología, Inmunología, Biotecnología y Genética, Universidad de Buenos Aires, Buenos Aires, Argentina.
Introduction: Polycystic Ovary Syndrome (PCOS) affects 5-20% of reproductive-aged women. Insulin resistance (IR) is common in PCOS with consequent elevated risks of metabolic disorders and cardiovascular mortality. PCOS and obesity are complex conditions associated with Metabolic Syndrome (MS), contributing to cardiovascular disease and type 2 diabetes mellitus (T2D).
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!