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Hic-5 regulates Src-induced invadopodia rosette formation and organization
Anushree C Gulvady1, Ian J Forsythe1, Christopher E Turner1
1Department of Cell and Developmental Biology, State University of New York Upstate Medical University, Syracuse, NY 13210.
Molecular Biology of the Cell
|March 21, 2019
Summary
Hic-5 protein is crucial for organizing invadopodia into matrix-degrading rosettes. This process is vital for tumor cell invasion and involves FAK kinase and actin dynamics.
Area of Science:
- Cell Biology
- Cancer Research
- Biochemistry
Background:
- Proto-oncogene Src-transformed fibroblasts form invadopodia that self-organize into matrix-degrading rosettes.
- The precise mechanisms governing invadopodia spatiotemporal reorganization into rosettes remain unclear.
Purpose of the Study:
- To investigate the role of Hic-5 in the formation and organization of invadopodia rosettes.
- To elucidate the molecular mechanisms underlying rosette formation and dynamics.
Main Methods:
- Live cell imaging and domain-mapping analysis of Hic-5.
- Pharmacological inhibition and mutant expression studies.
- Superresolution microscopy.
Main Results:
- Hic-5 is essential for rosette formation and organization in Src-transfected fibroblasts.
- FAK kinase activity, Rac1, formin, and myosin II are necessary for invadopodia dynamics and rosette coalescence.
- Formins FHOD1 and INF2 mediate F-actin fiber formation, potentially facilitating rosette assembly.
Conclusions:
- Hic-5 orchestrates invadopodia organization into rosettes, promoting localized matrix degradation.
- This mechanism is potentially significant for tumor cell invasion and metastasis.
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