No – Page 14 – Cell Stress

The targeting of tumor-associated macrophages by vaccination

Immune suppressive myeloid cells include a heterogenous population of cells that include tumor-associated macrophages (TAMs). TAMs are major players in inducing the immunosuppressive microenvironment associated with many tumors. These lesions … Read more

Constitutional Mosaic Epimutations – a hidden cause of cancer?

Silencing of tumor suppressor genes by promoter hypermethylation is a key mechanism to facilitate cancer progression in many malignancies. While promoter hypermethylation can occur at later stages of the carcinogenesis process, constitutional methylation of key tumor suppressors may be an initiating event whereby cancer is started. Constitutional BRCA1 methylation due to cis-acting germline genetic variants is associated with a high risk of breast and ovarian cancer. However, this seems to be a rare event, restricted to a very limited number of families. In contrast, mosaic constitutional BRCA1 methylation is detected in 4-7% of newborn females without germline BRCA1 mutations. While the cause of such methylation is poorly understood, mosaic normal tissue BRCA1 methylation is associated with a 2-3 fold increased risk of high-grade serous ovarian cancer (HGSOC). As such, BRCA1 methylation may be the cause of a significant number of ovarian cancers. Given the molecular similarities between HGSOC and basal-like breast cancer, the (…)

The role of keratins in modulating carcinogenesis via communication with cells of the immune system

The connection between inflammation and cancer has been well established; however, little is known about the underlying mechanisms in the context of keratin loss. Keratins belong to a large family … Read more

Mitochondrial stress delays tumorigenesis in a Li-Fraumeni syndrome mouse model

As a prominent hub of metabolic activity, the mitochondrion can initiate retrograde signaling in response to bioenergetic stress that is important for various adaptive changes including cell cycle regulation [1][2]. … Read more

Mitochondria organize the cellular proteostatic response and promote cellular senescence

Timely disposal and degradation of misfolded proteins and their aggregates is critical for cellular proteostasis and the well-being of a cell. During evolution, cells have acquired a sophisticated system to … Read more

The primary cilium protein folliculin is part of the autophagy signaling pathway to regulate epithelial cell size in response to fluid flow

Autophagy is a conserved molecular pathway directly involved in the degradation and recycling of intracellular components. Autophagy is associated with a response to stress situations, such as nutrients deficit, chemical toxicity, mechanical stress or microbial host defense. We have recently shown that primary cilium-dependent autophagy is important to control kidney epithelial cell size in response to fluid flow induced shear stress. Here we show that the ciliary protein folliculin (FLCN) actively participates to the signaling cascade leading to the stimulation of fluid flow-dependent autophagy upstream of the cell size regulation in HK2 kidney epithelial cells. The knockdown of FLCN induces a shortening of the primary cilium, inhibits the activation of AMPK and the recruitment of the autophagy protein ATG16L1 at the primary cilium. Altogether, our results suggest that FLCN (…)

Role of protein phosphatases PP1, PP2A, PP4 and Cdc14 in the DNA damage response

INTRODUCTION Cells are constantly suffering endogenous and exogenous stresses that affect the integrity of the genetic material. It has been estimated that every cell of our body is exposed to … Read more

Hepatic stress associated with pathologies characterized by disturbed glucose production

LIVER FUNCTION IN GLUCOSE PRODUCTION AND NORMOGLYCEMIA Maintaining normal glucose levels in the organism i.e. between 0.7 to 1.1 g/L, is a complex task, involving a multi-organ crosstalk responsible for … Read more

Could de-stressing the brain be the solution for long-term weight loss?

INTRODUCTION One just needs to take a look at a typical vending machine (often found in hospitals) to appreciate what has happened to our food and drink. The relatively sudden … Read more

Metabolic and functional reprogramming of myeloid-derived suppressor cells and their therapeutic control in glioblastoma

Glioblastoma, also known as glioblastoma multiforme, is the most common and deadliest form of high-grade malignant brain tumors with limited available treatments. Within the glioblastoma tumor microenvironment (TME), tumor cells, stromal cells, and infiltrating immune cells continuously interact and exchange signals through various secreted factors including cytokines, chemokines, growth factors, and metabolites. Simultaneously, they dynamically reprogram their metabolism according to environmental energy demands such as hypoxia and neo-vascularization. Such metabolic reprogramming can determine fates and functions of tumor cells as well as immune cells. Ultimately, glioma cells in the TME transform immune cells to suppress anti-tumor immune cells such as T, natural killer (NK) cells, and dendritic cells (DC), and evade immune surveillance, and even to promote (…)