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Extracellular cues drive integrin mediated signaling to drive cancer cell invasion

  • Author(s): Rubashkin, Matthew Gregory
  • Advisor(s): Weaver, Valerie M
  • et al.
Abstract

For several decades oncologists have been faced with the obstacle of properly classifying tumors for effective patient treatment. Traditionally, this was accomplished by documenting changes in cancer cells, and through observation of canonical changes to the extracellular matrix (ECM). However, even when I began my graduate studies in 2010, it was still unclear if cancer cells were driven to metastasize by changes to the ECM, or if changes to the ECM were a result of malignant progression. Over the past 5 years I have worked in Dr. Valerie Weaver’s laboratory at UCSF to answer how cancer cells interpret extracellular mechanical cues in 3D and how these cues can be translated into oncogenic signals at the cell-ECM interface. In order to study molecular interactions of oncogenic proteins in invasive cancer cells, I participated in the development of a new super-resolution microscopy technique, Scanning Angle Interference Microscopy (SAIM). I then employed this technology to determine how ECM stiffness and composition can drive vinculin mediated PI3-kinase signaling to enhance cell invasion, and studied how paxillin mediated mechano-sensing of the ECM could drive metastasis in difficult to treat triple negative breast cancer patients.

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