Indraneel Mittra
Tata Memorial Center, India
Title: Biology of cell-free nucleic acids and its role in initiation and metastasis of cancer
Biography
Biography: Indraneel Mittra
Abstract
Several hundred billion to a trillion cells die in the adult human body daily, and a considerable amount of fragmented cell-free nucleic acids (cfNAs) from dying cells are released into the circulation. Our research has shown that circulating cfNAs can freely enter into healthy cells, accumulate in their nuclei, trigger a DNA damage repair response (DDR) and integrate into host cell genomes by an unique mechanism.Similarly, at the tissue level, locally generated cfNAs from dead cells can be taken-up by healthy bystander cells to induce DDR that facilitates their integration into recipient cell genomes. Genomic integration of cfNAs leads to dsDNA breaks, inflammation, chromosomal instability, senescence and apoptosis of recipient cells. cfNAs from cancerous cells can cause oncogenic transformation of NIH3T3 cells which are tumourigenic in immune-deficient mice. These findings raise a new hypothesis of cancer metastasis which posits that metastasis arises from de novo oncogenic transformation of cells of target organs induced by cfNAs arising from apoptotic circulating tumour cells (CTCs). This hypothesis challenges the current dogma that metastasis are produced by growth of CTCs that are lodged in distant organs.
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