PART 2 : TME et ECM

Cancer cells can produce their own growth factors, making them independent of external signals.

Cancer cells downregulate E-cadherin, a protein that helps cells stick together, allowing them to break free and invade.

Overexpression of Bcl-2, a protein that protects cells from death, and downregulation of Bax and Bak, proteins that promote death, means cancer cells resist apoptosis.

A common mutation in cancer cells that prevents apoptosis by disrupting a key tumor suppressor gene.

Cancer cells overactivate telomerase, an enzyme that maintains chromosome ends, allowing them to divide indefinitely.

VEGF promotes the formation of new blood vessels, providing cancer cells with nutrients and oxygen for growth.

Cancer cells activate telomerase, which prevents them from dying off due to chromosome shortening. This allows them to replicate indefinitely, making them 'immortal'.

Cancer cells secrete MMPs that break down the ECM, allowing them to spread and invade surrounding tissues.

Loss of TGF-β signaling in cancer cells causes them to ignore anti-growth signals and continue dividing.

The MAPK pathway is a key regulator of cell growth and proliferation. It is altered in cancer cells, leading to uncontrolled growth signals.

Cancer cells mainly rely on glycolysis for energy, even in the presence of oxygen.

Cancer cells have a higher rate of glycolysis, consuming glucose to produce energy even when oxygen is available. This is in contrast to normal cells which primarily use oxidative phosphorylation.

Cancer cells have increased protein synthesis to support rapid growth and division.

The Warburg effect benefits cancer cells by allowing fast energy production, even though it's less efficient, to support their rapid growth and proliferation.

Cancer cells produce lactate as a byproduct of their high glycolytic activity.

GLUT1 is a protein that transports glucose into cells. It's upregulated in cancer cells to meet their high energy demands.

Cancer cells have increased anabolic activity due to upregulation of biosynthetic pathways like nucleotide synthesis, which helps create DNA and RNA for rapid cell division.

Cancer cells require high nutrient uptake to support their increased anabolic processes and rapid growth.

Cancer cells develop mechanisms to protect themselves from the damaging effects of reactive oxygen species (ROS) by enhancing their antioxidant systems.

HIF-1 is a transcription factor activated in low-oxygen conditions (hypoxia) in tumors. It induces the production of VEGF and other factors that support tumor survival and growth.

Chronic inflammation promotes angiogenesis, which supplies the tumor with oxygen and nutrients for growth.

Both cancer cells and inflammatory cells in the tumor microenvironment secrete MMPs which break down the ECM and promote invasion.

HIF-1, a transcription factor activated in hypoxic conditions, is constantly active in cancer environments, driving angiogenesis and tumor survival.

M1 macrophages are pro-inflammatory cells that help fight tumor progression.

ROS can cause DNA damage, leading to mutations and promoting tumor growth.

Innate immunity is the first line of defense against pathogens and involves cells like macrophages and neutrophils.

Dendritic cells are antigen-presenting cells that show pieces of pathogens to T cells.

Cytotoxic CD8+ T cells directly kill tumor cells by releasing cytotoxic substances.

Low oxygen in the tumor microenvironment (hypoxia) can lead to T cell exhaustion, making them less effective at fighting the tumor.

M1 macrophages are pro-inflammatory cells that help fight cancer by killing tumor cells and activating T cells.

In the immunosuppressive tumor microenvironment, macrophages switch to an M2 phenotype, which promotes tumor growth and suppresses the immune response.

B cells produce antibodies, which are specialized proteins that target specific invaders and help fight infection.

TGF-β can suppress the immune response, allowing the tumor to evade immune surveillance.

Regulatory T cells (Tregs) suppress the immune system to prevent autoimmune reactions. However, in cancer, they can suppress anti-tumor responses, promoting tumor growth.

Myeloid cells, a type of white blood cell, contribute to the early elimination of tumors by releasing anti-tumor signals and activating immune cells.

Collagen is the most abundant protein in the extracellular matrix, providing structural support and tensile strength to tissues.

MMPs can break down collagen and other components of the ECM, allowing cancer cells to breach tissues and spread.

Fibronectin and laminin are proteins in the ECM that provide adhesive support, helping cells bind and organize within tissues.

The ECM provides physical support for cells, regulates their communication and behavior, and can promote or hinder tumor growth and spread.

CAFs secrete TGF-β and FGF, which remodel the ECM to support tumor growth and spread.

CAFs deposit and stiffen the ECM, blocking immune cells from entering the tumor and fighting it.

TGF-β is a signaling molecule that can polarize fibroblasts into CAFs, causing them to contribute to tumor progression.

Increased collagen deposition in the ECM makes it stiffer, promoting tumor growth and hindering immune response.

Integrins are proteins that connect cells to the ECM and help regulate cell signaling and migration.

ECM remodeling, particularly by CAFs, can create pathways that allow cancer cells to break free from the tumor and spread to other locations in the body.

EMT involves a loss of cell-to-cell adhesion and increased motility, allowing cancer cells to move through tissues and metastasize.

TGF-β signaling is a major driver of EMT in cancer, inducing changes in cell behavior that enable invasion and metastasis.

Intravasion is the process of cancer cells breaking through the basement membrane and entering the surrounding blood or lymphatic vessels.

Mesenchymal migration, where cells move in an elongated shape, is the main mode of migration in solid tumors.

MMPs break down the ECM, helping cancer cells invade surrounding tissues and spread to distant locations.