Is autophagy good or bad for cancer?

However, autophagy promotes cancer progression in many cancers. Many studies demonstrate that autophagy supplies sufficient nutrients that enable cancer cell growth. However, some studies indicated that autophagy also suppresses tumor growth, initiation, and development.

Is autophagy a hallmark of cancer?

These cellular traits, which convert a normal cell to a malignant one, are considered the hallmarks of cancer [78, 79]. The aforementioned studies suggest that autophagy has context-dependent roles in cancer, and hence it has been associated with several hallmarks of cancer.

What triggers macropinocytosis?

Macropinocytosis is usually initiated by external stimulation. The stimulus is commonly in the form of growth factors that trigger activation of receptor tyrosine kinases (RTKs). These, in turn, activate a signalling cascade that induces changes in the dynamics of actin filaments and trigger plasma membrane ruffling.

How do you reduce macropinocytosis?

Scanning electron microscopy imaging indicated that imipramine inhibits membrane ruffle formation, a critical early step leading to initiation of macropinocytosis. Finally, imipramine has been shown to inhibit macropinocytosis in several cell types, including cancer cells, dendritic cells and macrophages.

How can autophagy make cancer worse?

Loss of Beclin-1 blocks activation of autophagy, and thus precludes its cytoprotective role. This impairment of degradation of potentially carcinogenic agents or damaged organelles leads to the spreading of damage inside cells and increases the risk of cancer development.

Can autophagy be bad?

So, Is It Good or Bad? Neither, it is an essential and ongoing cellular process that can be upregulated and downregulated. Both too much and too little autophagy have been associated with disease. Yet, it remains a valuable tool that can be manipulated for therapeutic purposes (1).

Does macropinocytosis use integrin?

Macropinocytosis is known to mediate the bulk uptake of membranes, fluid, and signaling receptors. Our findings suggest that macropinocytosis also can participate in the very rapid turnover of cell surface integrins, a pathway that is critical for stimulated cell migration.

Why does excessive macropinocytosis lead to cell death?

Macropinocytosis not only promotes cancer survival but also has harmful effects on cancers. During excessive stimulation of macropinocytosis in tumor cells, the balance of macropinocytosis is disrupted; macropinosomes gradually merge with each other and the extreme vacuole formation finally leads to cell death.

How do you induce macropinocytosis?

The macropinocytosis pathway, which is induced by cellular biological and environmental conditions, including related-receptor activation, oncogenic protein expression and pathogen invasion, is possibly associated with the cellular uptake of exosomes leading to cellular regulation and cell-to-cell communications.

What is the difference between phagocytosis and macropinocytosis?

Phagocytosis is an endocytic process in which opsonized particles bind to specific receptors on the DC surface and enter cells in membrane-derived phagosomes. Macropinocytosis mediates non-specific uptake of soluble antigens into the cell via macropinosomes.

Does coffee break autophagy?

Another study showed that consumption of both caffeinated and decaffeinated coffee trigger autophagy in mice, which is good news for longevity. The authors of this study related the increase in mTOR inhibition and other cellular processes to the polyphenols in coffee.

What does macropinocytosis do to a cancer cell?

Macropinocytic cancer cells scavenge amino acids from extracellular proteins. Here, we show that consuming necrotic cell debris via macropinocytosis (necrocytosis) offers additional anabolic benefits.

Why are tumor cells reliant on autophagy 2?

At the same time, nutrient delivery to tumor cells is limited by abnormal, leaky vasculature, and high interstitial pressure that collapses blood vessels, further compromising perfusion. These limitations make tumor cells reliant on the catabolic process of autophagy 2.

How does mTORC1 and mtor2 inhibit macropinocytosis?

The vacuoles then merge and rupture, killing the cells. We confirmed the inhibition of mTORC1/mTORC2 as the underpinning mechanism for macropinocytosis. Exposure to rapamycin, an mTORC1 inhibitor, or mTORC2 knockdown alone had little or reduced effect relative to the combination.

How does macropinocytosis provide resistance to therapies?

Amino acids provided by macropinocytosis might also confer resistance to therapies that increase the demand for nucleotides by fueling de novo nucleotide synthesis pathways. If macropinocytic cells could directly scavenge nucleotides, even greater protection might be observed because the energetic cost of nucleotide synthesis would be avoided.