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A Jnk-Rho-Actin remodeling positive feedback network directs Src-driven invasion

V A Rudrapatna1, E Bangi1, R L Cagan1

  • 1Department of Developmental and Regenerative Biology, Mount Sinai School of Medicine, New York, NY, USA.

Oncogene
|July 9, 2013
PubMed

Insights

Actin remodeling proteins (ARPs) are key regulators of tumor cell invasion. This study reveals ARPs are not just downstream effectors but actively participate in a feedback network with oncogenic pathways, driving cancer cell migration.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Cancer Research

Background:

  • Tumor cell invasion involves cytoskeletal dynamics orchestrated by signaling pathways like c-Jun N-terminal kinase (Jnk) and RhoGTPases.
  • Actin remodeling proteins (ARPs) are crucial for cytoskeletal changes during cell migration.
  • Src kinase is a significant factor in tumor aggression, metastasis, and patient mortality.

Purpose of the Study:

  • To elucidate the mechanisms by which Src regulates actin dynamics and promotes invasive cell migration.
  • To identify key mediators of invasion in a Drosophila model.

Main Methods:

  • A genetic modifier screen was conducted in a Drosophila model of tumor cell invasion.
  • The roles of identified genes in mediating invasion, oncogenic signaling, and pathway activation were investigated.

Main Results:

  • Nine genes associated with actin dynamics were identified as mediators of invasion.
  • Actin remodeling proteins (ARPs) were found to be essential for Src-driven oncogenic effects, including Mmp1 expression and apoptosis initiation.
  • ARPs were identified as regulators of Jnk pathway activity, with both Src and Rho1 activating Jnk in an ARP-dependent manner during invasion.

Conclusions:

  • Actin remodeling proteins (ARPs) are not merely downstream executors of oncogenic signaling.
  • ARPs are integral components of a positive feedback network involving canonical oncogenic pathways that promote tumor invasion.
  • These findings offer new insights into the complex interplay between cytoskeletal dynamics and cancer progression.

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