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An overview of kinin mediated events in cancer progression and therapeutic applications

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ELSEVIER
DOI: 10.1016/j.bbcan.2022.188807

Keywords

Bradykinin; Cancer metastasis; Tumor-microenvironment; Cancer signaling pathways; Cancer therapy

Funding

  1. CSIR-UGC India, Ministry of Human Resource Development (MHRD)
  2. Indian Institute of Technology Kharagpur, Indian Council of Medical Research (ICMR)
  3. Science and Engineering Research Board (SERB) India

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Kinins are bioactive peptides involved in cancer progression and inflammatory response. They activate kinin receptors and receptor tyrosine kinases to regulate multiple signaling pathways and contribute to cancer hallmarks. In the tumor microenvironment, kinins activate fibroblasts, interact with mesenchymal stem cells, and recruit immune cells. Kinin receptor antagonists show anti-metastatic potential.
Kinins are bioactive peptides generated in the inflammatory milieu of the tissue microenvironment, which is involved in cancer progression and inflammatory response. Kinins signals through activation of two G-protein coupled receptors; inducible Bradykinin Receptor B1 (B1R) and constitutive receptor B2 (B2R). Activation of kinin receptors and its cross-talk with receptor tyrosine kinases activates multiple signaling pathways, including ERK/MAPK, PI3K, PKC, and p38 pathways regulating cancer hallmarks. Perturbations of the kinin-mediated events are implicated in various aspects of cancer invasion, matrix remodeling, and metastasis. In the tumor microenvironment, kinins initiate fibroblast activation, mesenchymal stem cell interactions, and recruitment of immune cells. Albeit the precise nature of kinin function in the metastasis and tumor microenvironment are not completely clear yet, several kinin receptor antagonists show anti-metastatic potential. Here, we showcase an overview of the complex biology of kinins and their role in cancer pathogenesis and therapeutic aspects.

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