Dr. Razidlo's lab team has two main focus areas of research related to cancer metastasis:

  • Signaling pathways that regulate cytoskeletal remodeling
  • Signals from the tumor microenvironment

Our goal is to understand how tumor cells invade and spread, particularly in pancreatic cancer, with the hope of designing therapies to stop the spread of cancer and improve patient survival.

Signaling pathways that regulate cytoskeletal remodeling

Actin cytoskeletal dynamics

The dynamic actin cytoskeleton provides the structure for invasive protrusions. We're investigating the proteins that control actin polymerization, branching and bundling, and how they're activated in invasive cancer cells.

Activators of RhoGTPases

Actin cytoskeletal dynamics are controlled by the small GTPases Rac, Cdc42 and Rho. These GTPases are molecular switches that are regulated by associated proteins — activation by guanine nucleotide exchange factors (GEFs) and inactivation by guanine nucleotide associated proteins (GAPs).

We're particularly interested in how GEFs are aberrantly activated in pancreatic cancers and the consequence for migratory processes. We've described that Vav1, a GEF for Rac and Cdc42 that's turned on in pancreatic cancers, can activate the pro-invasive machinery to upregulate invasive migration. This suggests that Vav1 may also be a potent therapeutic target to inhibit metastasis.

Remodeling of the extracellular matrix

Tumor cells form degradative structures called invadopodia that serve as sites for degradation of the extracellular matrix by matrix metalloproteinases. Our lab is investigating the mechanisms by which tumor cells form these actin-based, degradative protrusions through the concerted action of cytoskeletal, membrane and trafficking dynamics.

In addition, we have found that stromal cells robustly degrade and remodel the extracellular matrix by distinct mechanisms. This emphasizes the need to understand the contributions of the complex tumor microenvironment to design effective therapies to halt pro-invasive ECM remodeling.

Signals from the tumor microenvironment

Cross-talk between tumor cells and the inflammatory microenvironment

Inflammatory signals are abundant in pancreatic tumors and can contribute to tumor progression and metastasis. Tumor cells also contribute to the inflammatory microenvironment, illustrating a complex cross-talk among cell types.

We're interested in how the inflammatory environment is modulated in pancreatic cancer and how inflammatory cytokines upregulate the invasive machinery in tumor cells.

Metastatic invasion fueled by excess stromal lipids

Tumor cells accumulate lipids by multiple mechanisms, via increased synthesis and via uptake from the microenvironment. How do tumor cells control the balance between lipid storage and catabolism? How are stored lipids subsequently utilized for invasive migration? We're particularly interested in how this metabolic rewiring is regulated by prominent oncogenes in pancreatic cancer.

Related publications

Research funding

We're grateful for research funding from these organizations: