Department of Molecular Physiology & Biophysics

University of Iowa


Research in the Henry Lab

Role of dystroglycan in prostate cancer progression

Cell-matrix interactions are known to play key roles in cancer progression and metastasis. Dystroglycan is a receptor for extracellular matrix proteins such as members of the laminin family and perlecan. A consistent finding in many cancers, including prostate cancer, is that glycosylation of the extracellular portion of dystroglycan, required for matrix ligand binding, does not occur normally. We have been exploring the molecular basis for altered dystroglycan glycosylation and the functional consequences of this during prostate cancer progression.

Epithelial-to-mesenchymal transition (EMT)
in prostate cancer metastasis

EMT is a normal process in development whereby epithelial cells change their identity to become mesenchymal in nature to facilitate cell migration in the embryo. Aspects of this process may be recapitulated in cancer progression and metastasis. We have found that transendothelial migration of prostate cancer cells, a model for how cancer cells may exit the vasculature, selects for cells that have undergone ZEB1-dependent EMT. Other studies are aimed at defining the consequences of EMT on cell-matrix interactions and metastasis in prostate cancer.

Circulating tumor cells

A more recently developed interest in the lab is related to circulating tumor cells (CTCs) which represent an intermediate stage of metastasis. CTCs encounter a very foreign microenvironment in the circulation, detached from matrix and solid tissue and exposed to hemodynamic forces. Very little is known about how this influences the biology of these cells. We have found that cancer cells are remarkably resistant to brief pulses of high level fluid shear forces that might be transiently encountered by CTCs. Resistance to fluid shear stress may distinguish malignant from benign epithelial cells. Moreover our work demonstrates a novel physiologic response to fluid shear stress exhibited by transformed cells that may facilitate metastatic dissemination.