How a Key Enzyme VEGFR1 Prevents Cancer?
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Source– This post on How a Key Enzyme Prevents Cancer has been created based on the article “Camouflaging as a dead enzyme VEGFR1 holds key to medical solutions for colon and renal cancers” published in “PIB” on 29 June 2024.

Why in the news?

Researchers have found the molecular mechanism by which a cell surface receptor which is a part of a family of enzymes that bind to growth factors helps prevent cancer. This enzyme VEGFR1 plays a crucial role in regulating cell growth, differentiation, survival, metabolism, and migration.

About VEGFR1

VEGFR 1
Source: PIB

1. VEGFR1 (Vascular Endothelial Growth Factor Receptor 1) is a type of cell surface receptor known as a Receptor Tyrosine Kinase (RTK).

2. RTKs are essential for converting external signals (like growth factors) into cellular responses. These responses include cell growth, development, and immune functions.

3. When a ligand (such as a hormone) binds to VEGFR1, it activates an enzyme inside the cell that triggers a series of reactions necessary for these functions.

Key Findings of the Research

1. Autoinhibition of VEGFR1: VEGFR1 can keep itself inactive (autoinhibited) when there is no ligand present. This self-inhibition prevents unwanted cell growth and division, which is crucial for preventing cancer.

2. Difference Between VEGFR1 and VEGFR2: The study highlighted the difference between VEGFR1 and VEGFR2. Unlike VEGFR1, VEGFR2 can become spontaneously active without a ligand, which can lead to problems like uncontrolled cell growth. However, VEGFR1 remains inactive even when overexpressed, making it a safer option for controlling cell functions.

3. Ionic Latch Mechanism: The research team discovered a unique ionic latch in VEGFR1. This latch keeps the enzyme inactive by stabilizing its auto-inhibited state. The latch hooks a part of the enzyme called the juxtamembrane segment onto the kinase domain, preventing unwanted activation.

4. Role of Cellular Tyrosine Phosphatase: The study proposed that cellular tyrosine phosphatase plays a crucial role in modulating VEGFR1 activity. By regulating this activity, it’s possible to control the formation of new blood vessels (angiogenesis), which is essential in cancer treatment.

Significance of the Research

1. Potential Cancer Treatments: By understanding how VEGFR1 stays inactive, scientists can explore new ways to treat cancer. They can develop therapies that use special molecules to keep VEGFR1 in its inactive state. This can help treat cancers like colon and kidney cancer, where VEGFR1 is often too active.

2. Preventing Uncontrolled Cell Growth: Keeping VEGFR1 inactive is important because it helps prevent unwanted cell growth. When VEGFR1 gets activated without control, it can lead to cancers, diabetes, and autoimmune diseases. Controlling VEGFR1 helps maintain healthy cell functions.

3. New Treatment Methods: The research shows that using molecules called phosphatase modulators to control VEGFR1 activity could be a promising treatment. This method can help manage conditions caused by VEGFR1 getting activated on its own, leading to better treatments for these diseases.

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