4.5 Article

scribble (scrib) knockdown induces tumorigenesis by modulating Drp1-Parkin mediated mitochondrial dynamics in the wing imaginal tissues of Drosophila

Journal

MITOCHONDRION
Volume 44, Issue -, Pages 103-110

Publisher

ELSEVIER SCI LTD
DOI: 10.1016/j.mito.2018.01.006

Keywords

scribble; Drp-1; Parkin; Mitochondria; Cancer; Drosophila

Funding

  1. Science and Engineering Research Board, India [P07/598]
  2. SERB [SERB/EMEQ-389/2014]
  3. ICMR
  4. DST-PURSE

Ask authors/readers for more resources

scrib loss of function is associated with various human-cancers. Most of the human-cancers have been characterized by mitochondrial dysfunction with elevated oxidative stress. However, the role of scrib to mitochondrial dysfunction in cancer has not been investigated earlier. Here, we have shown that scrib knockdown leads to mitochondrial depolarization, fragmentation and perinuclear-clustering along with disruption of the redox homeostasis. Moreover, the scrib abrogated tumor showed the elevation of Drp-1 and reduced expression of Marf, which suggests enhanced mitochondrial-fission. Further, the reduced expression of Parkin and HtrA2 interpret defective mitophagy leading to clustering of fragmented mitochondria and apoptotic inhibition in scrib knockdown tumors. Also, Parkin immunostaining depicted its reduced expression and mislocalization in the tumor cells in comparison to wild type. Moreover, the genetic study revealed the epistatic interactions of parkin and scrib. Thus, for the first time our results suggested that scrib loss induced mitochondrial-dysfunction modulates cancer progression by altering the mitochondrial dynamics regulators.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.5
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available