MEG8 as an antagonistic pleiotropic mechanism in breast cancer.

Cellular senescence connects aging and cancer. Cellular senescence is a common program activated by cells in response to various types of stress. During this process, cells lose their proliferative capacity and undergo distinct morphological and metabolic changes.

Protein homeostasis maintained by HOOK1 levels promotes the tumorigenic and stemness properties of ovarian cancer cells through reticulum stress and autophagy.

Background: Ovarian cancer has a high mortality rate mainly due to its resistance to currently used therapies. This resistance has been associated with the presence of cancer stem cells (CSCs), interactions with the microenvironment, and intratumoral heterogeneity. Therefore, the search for new therapeutic targets, particularly those targeting CSCs, is important for improving patient prognosis.

Hypoxia-induced immortalization of primary cells depends on Tfcp2L1 expression.

Cellular senescence is a stress response mechanism that induces proliferative arrest. Hypoxia can bypass senescence and extend the lifespan of primary cells, mainly by decreasing oxidative damage. However, how hypoxia promotes these effects prior to malignant transformation is unknown.

Essential role of PLD2 in hypoxia-induced stemness and therapy resistance in ovarian tumors.

Background: Hypoxia in solid tumors is an important source of chemoresistance that can determine poor patient prognosis. Such chemoresistance relies on the presence of cancer stem cells (CSCs), and hypoxia promotes their generation through transcriptional activation by HIF transcription factors.

Methods: We used ovarian cancer (OC) cell lines, xenograft models, OC patient samples, transcriptional databases, induced pluripotent stem cells (iPSCs) and Assay for Transposase-Accessible Chromatin using sequencing (ATAC-seq).

Phase II trial of CDK4/6 inhibitor palbociclib in advanced sarcoma based on mRNA expression of CDK4/ CDKN2A.

Cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitors demonstrated activity in terms of progression-free survival (PFS) in advanced dedifferentiated liposarcoma (DD-LPS), a sarcoma with CDK4 amplification. CDK4 overexpression is by far more common than amplification in sarcomas and it might be a rational target for CDK inhibitors. Preclinical investigators of this study found that CDK4 overexpression, while not of CDKN2A, was the most consistent predictive factor for palbociclib efficacy in sarcomas.

Inhibition of HSP90 in Driver Oncogene-Defined Lung Adenocarcinoma Cell Lines: Key Proteins Underpinning Therapeutic Efficacy.

The use of 90 kDa heat shock protein (HSP90) inhibition as a therapy in lung adenocarcinoma remains limited due to moderate drug efficacy, the emergence of drug resistance, and early tumor recurrence. The main objective of this research is to maximize treatment efficacy in lung adenocarcinoma by identifying key proteins underlying HSP90 inhibition according to molecular background, and to search for potential biomarkers of response to this therapeutic strategy. Inhibition of the HSP90 chaperone was evaluated in different lung adenocarcinoma cell lines representing the most relevant molecular alterations (EGFR mutations, KRAS mutations, or EML4-ALK translocation) and wild-type genes found in each tumor subtype.

Interactions of circadian clock genes with the hallmarks of cancer.

The molecular machinery of the circadian clock regulates the expression of many genes and processes in the organism, allowing the adaptation of cellular activities to the daily light-dark cycles. Disruption of the circadian rhythm can lead to various pathologies, including cancer. Thus, disturbance of the normal circadian clock at both genetic and environmental levels has been described as an independent risk factor for cancer.

NAD pool as an antitumor target against cancer stem cells in head and neck cancer.

Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous group of tumors that affect different anatomical locations. Despite this heterogeneity, HNSCC treatment depends on the anatomical location, TNM stage and resectability of the tumor. Classical chemotherapy is based on platinum-derived drugs (cisplatin, carboplatin and oxaliplatin), taxanes (docetaxel, paclitaxel) and 5-fluorouracil.

Role of the Hypoxic-Secretome in Seed and Soil Metastatic Preparation.

During tumor growth, the delivery of oxygen to cells is impaired due to aberrant or absent vasculature. This causes an adaptative response that activates the expression of genes that control several essential processes, such as glycolysis, neovascularization, immune suppression, and the cancer stemness phenotype, leading to increased metastasis and resistance to therapy. Hypoxic tumor cells also respond to an altered hypoxic microenvironment by secreting vesicles, factors, cytokines and nucleic acids that modify not only the immediate microenvironment but also organs at distant sites, allowing or facilitating the attachment and growth of tumor cells and contributing to metastasis.

Chronotherapy: Circadian Rhythms and Their Influence in Cancer Therapy.

Living organisms present rhythmic fluctuations every 24 h in their behavior and metabolism to anticipate changes in the environment. These fluctuations are controlled by a very complex molecular mechanism, the circadian clock, that regulates the expression of multiple genes to ensure the right functioning of the body. An individual's circadian system is altered during aging, and this is related to numerous age-associated pathologies and other alterations that could contribute to the development of cancer.

Nicotinamide Adenine Dinucleotide (NAD) Metabolism as a Relevant Target in Cancer.

NAD+ is an important metabolite in cell homeostasis that acts as an essential cofactor in oxidation-reduction (redox) reactions in various energy production processes, such as the Krebs cycle, fatty acid oxidation, glycolysis and serine biosynthesis. Furthermore, high NAD+ levels are required since they also participate in many other nonredox molecular processes, such as DNA repair, posttranslational modifications, cell signalling, senescence, inflammatory responses and apoptosis. In these nonredox reactions, NAD+ is an ADP-ribose donor for enzymes such as sirtuins (SIRTs), poly-(ADP-ribose) polymerases (PARPs) and cyclic ADP-ribose (cADPRs).

Molecular Radiobiology in Non-Small Cell Lung Cancer: Prognostic and Predictive Response Factors.

Non-small-cell lung cancer (NSCLC) is the leading cause of cancer-related death worldwide, generating huge economic and social impacts that have not slowed in recent years. Oncological treatment for this neoplasm usually includes surgery, chemotherapy, treatments on molecular targets and ionizing radiation. The prognosis in terms of overall survival (OS) and the different therapeutic responses between patients can be explained, to a large extent, by the existence of widely heterogeneous molecular profiles.

A Six-Gene Prognostic and Predictive Radiotherapy-Based Signature for Early and Locally Advanced Stages in Non-Small-Cell Lung Cancer.

Non-small-cell lung cancer (NSCLC) is the leading cause of cancer death worldwide, generating an enormous economic and social impact that has not stopped growing in recent years. Cancer treatment for this neoplasm usually includes surgery, chemotherapy, molecular targeted treatments, and ionizing radiation. The prognosis in terms of overall survival (OS) and the disparate therapeutic responses among patients can be explained, to a great extent, by the existence of widely heterogeneous molecular profiles.

Senotherapeutics in Cancer and HIV.

Cellular senescence is a stress-response mechanism that contributes to homeostasis maintenance, playing a beneficial role during embryogenesis and in normal adult organisms. In contrast, chronic senescence activation may be responsible for other events such as age-related disorders, HIV and cancer development. Cellular senescence activation can be triggered by different insults.

3D and organoid culture in research: physiology, hereditary genetic diseases and cancer.

In nature, cells reside in tissues subject to complex cell-cell interactions, signals from extracellular molecules and niche soluble and mechanical signaling. These microenvironment interactions are responsible for cellular phenotypes and functions, especially in normal settings. However, in 2D cultures, where interactions are limited to the horizontal plane, cells are exposed uniformly to factors or drugs; therefore, this model does not reconstitute the interactions of a natural microenvironment.

SPINOPHILIN: A multiplayer tumor suppressor.

SPINOPHILIN (SPN, PPP1R9B or NEURABIN-2) is a multifunctional protein that regulates protein-protein interactions in different cell signaling pathways. SPN is also one of the regulatory subunits of protein phosphatase 1 (PP1), implicated in the dephosphorylation of retinoblastoma protein (pRB) during cell cycle. The gene has been described as a tumor suppressor in different human tumor contexts, in which low levels of SPN are correlated with a higher grade and worse prognosis.

Leveraging Genomics, Transcriptomics, and Epigenomics to Understand the Biology and Chemoresistance of Ovarian Cancer.

Ovarian cancer is a major cause of fatality due to a gynecological malignancy. This lethality is largely due to the unspecific clinical manifestations of ovarian cancer, which lead to late detection and to high resistance to conventional therapies based on platinum. In recent years, we have advanced our understanding of the mechanisms provoking tumor relapse, and the advent of so-called omics technologies has provided exceptional tools to evaluate molecular mechanisms leading to therapy resistance in ovarian cancer.

Empty spiracles homeobox genes EMX1 and EMX2 regulate WNT pathway activation in sarcomagenesis.

Background: Sarcomas are a very heterogeneous group of tumors with intrinsic developmental programs derived from the cell of origin. This implies a functional hierarchy inside tumors governed by sarcoma stem cells. Therefore, genetic and/or epigenetic changes profoundly affect the biology of sarcoma tumor stem cells.

Cellular senescence or stemness: hypoxia flips the coin.

Cellular senescence is a complex physiological state whose main feature is proliferative arrest. Cellular senescence can be considered the reverse of cell immortalization and continuous tumor growth. However, cellular senescence has many physiological functions beyond being a putative tumor suppressive trait.

Role of the Holoenzyme PP1-SPN in the Dephosphorylation of the RB Family of Tumor Suppressors During Cell Cycle.

Cell cycle progression is highly regulated by modulating the phosphorylation status of the retinoblastoma protein (pRB) and the other two members of the RB family, p107 and p130. This process is controlled by a balance in the action of kinases, such as the complexes formed by cyclin-dependent kinases (CDKs) and cyclins, and phosphatases, mainly the protein phosphatase 1 (PP1). However, while the phosphorylation of the RB family has been largely studied, its dephosphorylation is less known.