Advancing rhodium nanoparticle-based photodynamic cancer therapy: quantitative proteomics and assessment reveal mechanisms targeting tumor metabolism, progression and drug resistance.

Rhodium nanoparticles have been recently discovered as good photosensitizers with great potential in cancer photodynamic therapy by effectively inducing cytotoxicity in cancer cells under near-infrared laser. This study evaluates the molecular mechanisms underlying such antitumoral effect through quantitative proteomics. The results revealed that rhodium nanoparticle-based photodynamic therapy disrupts tumor metabolism by downregulating key proteins involved in ATP synthesis and mitochondrial function, leading to compromised energy production.

SUMOylation regulates the aggressiveness of breast cancer-associated fibroblasts.

Background: Cancer-associated fibroblasts (CAFs) are the most abundant stromal cellular component in the tumor microenvironment (TME). CAFs contribute to tumorigenesis and have been proposed as targets for anticancer therapies. Similarly, dysregulation of SUMO machinery components can disrupt the balance of SUMOylation, contributing to tumorigenesis and drug resistance in various cancers, including breast cancer.

Mechanistic insights into the antitumoral potential and in vivo antiproliferative efficacy of a silver-based core@shell nanosystem.

This study delves into the biomolecular mechanisms underlying the antitumoral efficacy of a hybrid nanosystem, comprised of a silver core@shell (Ag@MSNs) functionalized with transferrin (Tf). Employing a SILAC proteomics strategy, we identified over 150 de-regulated proteins following exposure to the nanosystem. These proteins play pivotal roles in diverse cellular processes, including mitochondrial fission, calcium homeostasis, endoplasmic reticulum (ER) stress, oxidative stress response, migration, invasion, protein synthesis, RNA maturation, chemoresistance, and cellular proliferation.

Cabergoline as a Novel Strategy for Post-Pregnancy Breast Cancer Prevention in Mice and Human.

Post-pregnancy breast cancer often carries a poor prognosis, posing a major clinical challenge. The increasing trend of later-life pregnancies exacerbates this risk, highlighting the need for effective chemoprevention strategies. Current options, limited to selective estrogen receptor modulators, aromatase inhibitors, or surgical procedures, offer limited efficacy and considerable side effects.

POTEE promotes breast cancer cell malignancy by inducing invadopodia formation through the activation of SUMOylated Rac1.

The small GTPase Rac1 (Ras-related C3 botulinum toxin substrate 1) has been implicated in cancer progression and in the poor prognosis of various types of tumors. Rac1 SUMOylation occurs during epithelial-mesenchymal transition (EMT), and it is required for tumor cell migration and invasion. Here we identify POTEE (POTE Ankyrin domain family member E) as a novel Rac1-SUMO1 effector involved in breast cancer malignancy that controls invadopodium formation through the activation of Rac1-SUMO1.

NCAPH Drives Breast Cancer Progression and Identifies a Gene Signature that Predicts Luminal A Tumor Recurrence.

Despite their generally favorable prognosis, luminal A tumors paradoxically pose the highest ten-year recurrence risk among breast cancers. From those that relapse, a quarter of them do it within five years after diagnosis. Identifying such patients is crucial, as long-term relapsers could benefit from extended hormone therapy, whereas early relapsers may require aggressive treatment.

Intermediate molecular phenotypes to identify genetic markers of anthracycline-induced cardiotoxicity risk.

Cardiotoxicity due to anthracyclines (CDA) affects cancer patients, but we cannot predict who may suffer from this complication. CDA is a complex disease whose polygenic component is mainly unidentified. We propose that levels of intermediate molecular phenotypes in the myocardium associated with histopathological damage could explain CDA susceptibility; so that variants of genes encoding these intermediate molecular phenotypes could identify patients susceptible to this complication.

Evolutionary Origins of Metabolic Reprogramming in Cancer.

Metabolic changes that facilitate tumor growth are one of the hallmarks of cancer. These changes are not specific to tumors but also take place during the physiological growth of tissues. Indeed, the cellular and tissue mechanisms present in the tumor have their physiological counterpart in the repair of tissue lesions and wound healing.

TRIB1 regulates tumor growth via controlling tumor-associated macrophage phenotypes and is associated with breast cancer survival and treatment response.

Molecular mechanisms that regulate tumor-associated macrophage (TAM) phenotype and function are incompletely understood. The pseudokinase TRIB1 has been reported as a regulator of macrophage phenotypes, both in mouse and human systems. Bioinformatic analysis was used to investigate the link between expression in breast cancer and therapeutic response to chemotherapy.

Pathophysiological Integration of Metabolic Reprogramming in Breast Cancer.

Metabolic changes that facilitate tumor growth are one of the hallmarks of cancer. The triggers of these metabolic changes are located in the tumor parenchymal cells, where oncogenic mutations induce an imperative need to proliferate and cause tumor initiation and progression. Cancer cells undergo significant metabolic reorganization during disease progression that is tailored to their energy demands and fluctuating environmental conditions.

The Pseudokinase TRIB3 Negatively Regulates the HER2 Receptor Pathway and Is a Biomarker of Good Prognosis in Luminal Breast Cancer.

Background: Tribbles pseudokinase 3 (TRIB3) has been proposed to both promote and restrict cancer generation and progression. However, the precise mechanisms that determine this dual role of TRIB3 in cancer remain to be understood. In this study we aimed to investigate the role of TRIB3 in luminal breast cancer, the most frequent subtype of this malignancy.

Inhibition of RAC1 activity in cancer associated fibroblasts favours breast tumour development through IL-1β upregulation.

Cancer-associated fibroblasts (CAFs) are highly abundant stromal components in the tumour microenvironment. These cells contribute to tumorigenesis and indeed, they have been proposed as a target for anti-cancer therapies. Similarly, targeting the Rho-GTPase RAC1 has also been suggested as a potential therapeutic target in cancer.

Synthesis and Evaluation of Ginkgolic Acid Derivatives as SUMOylation Inhibitors.

SUMOylation has emerged as an important post-translational modification that has been shown to modulate protein activity associated with various signaling pathways, and consequently, it has emerged as an important therapeutic target. While several natural products have been shown to inhibit enzymes involved in the SUMOylation process, there has been little progress toward the development of more selective and potent SUMOylation inhibitors. Ginkgolic acid was one of the first natural products discovered to inhibit the SUMO E1 enzyme.

Stromal SNAI2 Is Required for ERBB2 Breast Cancer Progression.

SNAI2 overexpression appears to be associated with poor prognosis in breast cancer, yet it remains unclear in which breast cancer subtypes this occurs. Here we show that excess SNAI2 is associated with a poor prognosis of luminal B HER2/ERBB2 breast cancers in which SNAI2 expression in the stroma but not the epithelium correlates with tumor proliferation. To determine how stromal SNAI2 might influence HER2 tumor behavior, -deficient mice were crossed with a mouse line carrying the protooncogene to generate HER2/ERBB2 breast cancer.

Inhibiting SUMO1-mediated SUMOylation induces autophagy-mediated cancer cell death and reduces tumour cell invasion via RAC1.

Post-translational modifications directly control protein activity and, thus, they represent an important means to regulate the responses of cells to different stimuli. Protein SUMOylation has recently been recognised as one such modification, and it has been associated with various diseases, including different types of cancer. However, the precise way that changes in SUMOylation influence the tumorigenic properties of cells remains to be fully clarified.

Lung Surfactant Lipids Provide Immune Protection Against Respiratory Infection.

Non-typeable (NTHi) causes persistent respiratory infections in patients with chronic obstructive pulmonary disease (COPD), probably linked to its capacity to invade and reside within pneumocytes. In the alveolar fluid, NTHi is in contact with pulmonary surfactant, a lipoprotein complex that protects the lung against alveolar collapse and constitutes the front line of defense against inhaled pathogens and toxins. Decreased levels of surfactant phospholipids have been reported in smokers and patients with COPD.

Supplementary data for the biological age linked to oxidative stress modifies breast cancer aggressiveness.

The data presented in this article are related to the research paper entitled "The biological age linked to oxidative stress modifies breast cancer aggressiveness" (M.M. Sáez-Freire, A.

The biological age linked to oxidative stress modifies breast cancer aggressiveness.

The incidence of breast cancer increases with age until menopause, and breast cancer is more aggressive in younger women. The existence of epidemiological links between breast cancer and aging indicates that both processes share some common mechanisms of development. Oxidative stress is associated with both cancer susceptibility and aging.

Activation of the orphan receptor GPR55 by lysophosphatidylinositol promotes metastasis in triple-negative breast cancer.

The orphan G protein-coupled receptor GPR55 has been directly or indirectly related to basic alterations that drive malignant growth: uncontrolled cancer cell proliferation, sustained angiogenesis, and cancer cell adhesion and migration. However, little is known about the involvement of this receptor in metastasis. Here, we show that elevated GPR55 expression in human tumors is associated with the aggressive basal/triple-negative breast cancer population, higher probability to develop metastases, and therefore poor patient prognosis.

Missing heritability of complex diseases: Enlightenment by genetic variants from intermediate phenotypes.

Diseases of complex origin have a component of quantitative genetics that contributes to their susceptibility and phenotypic variability. However, after several studies, a major part of the genetic component of complex phenotypes has still not been found, a situation known as "missing heritability." Although there have been many hypotheses put forward to explain the reasons for the missing heritability, its definitive causes remain unknown.

Unraveling heterogeneous susceptibility and the evolution of breast cancer using a systems biology approach.

Background: An essential question in cancer is why individuals with the same disease have different clinical outcomes. Progress toward a more personalized medicine in cancer patients requires taking into account the underlying heterogeneity at different molecular levels.

Results: Here, we present a model in which there are complex interactions at different cellular and systemic levels that account for the heterogeneity of susceptibility to and evolution of ERBB2-positive breast cancers.

Hace1 controls ROS generation of vertebrate Rac1-dependent NADPH oxidase complexes.

The Hace1-HECT E3 ligase is a tumor suppressor that ubiquitylates the activated GTP-bound form of the Rho family GTPase Rac1, leading to Rac1 proteasomal degradation. Here we show that, in vertebrates, Hace1 targets Rac1 for degradation when Rac1 is localized to the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase holoenzyme. This event blocks de novo reactive oxygen species generation by Rac1-dependent NADPH oxidases, and thereby confers cellular protection from reactive oxygen species-induced DNA damage and cyclin D1-driven hyper-proliferation.