IAS Gyan

Daily News Analysis


1st July, 2024 Science and Technology


Source: pib

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  • Recent research by scientists at the Indian Institute of Science Education and Research (IISER), Kolkata, has uncovered a novel approach to treating colon and renal cancers by targeting the vascular endothelial growth factor receptor 1 (VEGFR1).


  • This receptor, which typically regulates cell differentiation, proliferation, survival, metabolism, and migration, can withhold its activity in the absence of ligands, making it a promising target for therapeutic intervention.

Key Findings

  • Autoinhibition of VEGFR1: VEGFR1 remains in an inactive state without a ligand, a mechanism known as autoinhibition. This is due to a unique ionic latch present only in VEGFR1, which hooks the juxtamembrane segment onto the kinase domain, stabilizing the receptor in its autoinhibited conformation.
  • Differential Behavior of VEGFR1 and VEGFR2: While VEGFR2 can be spontaneously activated without its ligand, VEGFR1 cannot. VEGFR1 binds to its ligand, VEGF-A, with ten-fold higher affinity than VEGFR2, leading to transient kinase activation.
  • Implications for Cancer: Activation of VEGFR1 has been linked to cancer-associated pain, tumor cell survival in breast cancer, and the migration of human colorectal cancer cells. Therefore, stabilizing VEGFR1 in its autoinhibited state could prevent these pathological processes.
  • Role of Cellular Tyrosine Phosphatase: Researchers have proposed that cellular tyrosine phosphatase plays a crucial role in modulating VEGFR1 activity, highlighting the therapeutic potential of phosphatase modulators in regulating VEGFR1-mediated angiogenesis, which is crucial for cancer progression.

About VEGFR1

  • Vascular Endothelial Growth Factor Receptor 1 (VEGFR1), also known as Flt-1, is a tyrosine kinase receptor involved in the regulation of angiogenesis, vasculogenesis, and the permeability of blood vessels.
  • It is one of three receptors for the Vascular Endothelial Growth Factor (VEGF) family of ligands, the others being VEGFR2 (Flk-1/KDR) and VEGFR3 (Flt-4).
  • VEGFR1 is expressed in a variety of cell types, including:
  • Endothelial cells
  • Monocytes/Macrophages
  • Hematopoietic stem cells
  • The primary functions of VEGFR1 include:
  • Regulation of Angiogenesis: Though its role in angiogenesis is complex and context-dependent, VEGFR1 can act as a decoy receptor to modulate the availability of VEGF-A for VEGFR2, thereby controlling angiogenic signaling.
  • Monocyte/Macrophage Function: VEGFR1 plays a significant role in the migration and activation of monocytes and macrophages.
  • Hematopoiesis: Influences the mobilization and recruitment of hematopoietic stem cells.




Q. VEGFR1 is a critical regulator of angiogenesis, immune cell function, and hematopoiesis. Discuss. (10 marks)