Indian origin Researchers from The University of Texas MD Anderson Cancer Center demonstrated the dual role of VHL in apoptotic cancer stem cells that determine life and death decisions through the blebbishield emergency program.
(Image Credit: Dr. Goodwin G. Jinesh)
In our body, somatic cells are born by mitosis and almost all will die by apoptosis. Apoptosis is a physiological process in our body where the death of cells occurs as a normal and controlled part of an organism's growth or development. Researchers have been trying to develop the therapy to promote the death of cancer cells without causing damage to normal cells. Understanding of how cancer cells actually manage to escape apoptosis could be an answer to selectively kill these cancer cells.
Indian origin researchers Dr. Goodwin G. Jinesh, PhD., and Prof. Ashish M. Kamat, MD, MBBS, FACS, from Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA have demonstrated that cancer stem cells override apoptotic death after commencement of apoptosis by blebbishield emergency program. The study was published in the journal “Cell Death Discovery”.
Blebbishield emergency program constructs blebbishields from apoptotic bodies by stimulating robust dynamin-dependent endocytosis to drive cellular transformation. “The role of VHL in endocytosis and metastasis sparked the idea that VHL could be involved in blebbishield emergency program, despite it is a well-known tumor suppressor in renal cell carcinoma,” said the Investigators.
VHL is a well-known tumor suppressor and it often behaves like oncogene and the reasons behind such contradictory functions were not clearly demonstrated to date. The investigators have shown for the first time that the isoform length matters i.e., the short p19-VHL isoform acts as an oncogene by interacting specifically with RalBP1 during blebbishield formation, whereas the expression of long isoform p30-VHL correlates with inhibition of blebbishield emergency program. The researchers also tracked the VHL target genes that are differentially expressed during blebbishield emergency program and find that an oxidative stress management gene network is in action to execute blebbishield emergency program.
The Recent study suggests that improved understanding of the endocytosis regulators acting during the blebbishield emergency program is necessary to shed light on human tumorigenesis and develop therapeutics to block blebbishield emergency program.
VHL is a gene that is disabled in renal cell carcinoma. In the age of CRISPR/Cas9 human gene-editing, the recent study sheds light on the fact that which isoform one should opt for CRISPR/Cas9 editing and which isoform shouldn't be opted. The researchers are positive that, this will be useful in multiple cancer types including bladder cancer.
Since VHL is demonstrated as both tumor suppressor gene and oncogene promoting metastasis in an isoform-dependent manner, the isoform length gains wide medical and scientific interest to aid the development of cancer therapies.