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scribble (scrib) knockdown induces tumorigenesis by modulating Drp1-Parkin mediated mitochondrial dynamics in the

Amarish Kumar Yadav1, Saripella Srikrishna1

  • 1Cancer and Neurobiology Laboratory, Department of Biochemistry, Institute of Science, Banaras Hindu University, Varanasi 221005, India.

Mitochondrion
|January 24, 2018
PubMed

Insights

Loss of scrib protein function in cancer cells disrupts mitochondrial health, leading to increased fragmentation and impaired mitophagy. This mitochondrial dysfunction, driven by altered dynamics, significantly influences cancer progression.

Area of Science:

  • Oncology
  • Cell Biology
  • Mitochondrial Biology

Background:

  • Loss of scrib function is linked to human cancers.
  • Cancer is often associated with mitochondrial dysfunction and oxidative stress.
  • The specific role of scrib in cancer-related mitochondrial dysfunction remains unexplored.

Purpose of the Study:

  • To investigate the role of scrib in mitochondrial dysfunction within cancer.
  • To elucidate how scrib loss impacts mitochondrial dynamics and mitophagy in cancer progression.

Main Methods:

  • Utilized scrib knockdown models in cancer.
  • Assessed mitochondrial parameters: depolarization, fragmentation, and clustering.
  • Analyzed expression levels of key mitochondrial dynamics proteins (Drp-1, Marf) and mitophagy regulators (Parkin, HtrA2).
  • Performed Parkin immunostaining and genetic interaction studies.

Main Results:

  • Scrib knockdown induced mitochondrial depolarization, fragmentation, and perinuclear clustering.
  • Disrupted redox homeostasis was observed in scrib-deficient cells.
  • Elevated Drp-1 and reduced Marf indicated enhanced mitochondrial fission.
  • Reduced Parkin and HtrA2 suggested defective mitophagy, leading to fragmented mitochondria clustering.
  • Parkin showed reduced expression and mislocalization in tumor cells.
  • Genetic studies confirmed epistatic interactions between parkin and scrib.

Conclusions:

  • Scrib loss triggers significant mitochondrial dysfunction by altering mitochondrial dynamics.
  • Impaired mitophagy and altered fission/fusion balance contribute to cancer progression in scrib-deficient tumors.
  • This study establishes a novel link between scrib, mitochondrial dynamics, and cancer pathogenesis.
Keywords:
CancerDrosophilaDrp-1MitochondriaParkinscribble

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