investigator_user investigator user funding collaborators pending menu bell message arrow_up arrow_down filter layers globe marker add arrow close download edit facebook info linkedin minus plus save share search sort twitter remove user-plus user-minus
  • Project leads
  • Collaborators

Elucidation of the role of the RhoGEF Lfc in human epithelial tumors

Robert Rottapel

0 Collaborator(s)

Funding source

Canadian Institutes of Health Research (CIHR)
This proposal investigates an enzyme that controls the way a cell is shaped and the way it moves. We have discovered that this enzyme called Lfc, is important in cancer initiation and/or progression. A normal break down product of the membranes of our cells is called lysophosphatidic acid or LPA. LPA can function like a growth factor for cells. It can stimulate cells to survive under low nutrient conditions and induce cells to grow, change shape and become motile. LPA is an important growth factor created by our own bodies that can potently stimulate cancer growth. LPA levels are extremely high in certain types of tumors specifically ovarian, breast and colon. LPA binds to protein receptors on the cell surface which then activates biochemical cascades within the cell to instruct the cell to change. We have discovered that Lfc is one of the enzymes that is activated by LPA. We have shown that Lfc must be present in a cell in order for it to respond to LPA. We have examined over 200 ovarian cancers and discovered that Lfc is abnormally expressed at high levels. This means that not only is LPA elevated in patients with ovarian cancer but so is the machinery inside the cell necessary to activate the pathway that make the cell grow and move. We propose to analyze how Lfc is normally controlled in the cell. What turns it on, what turns it off? We have discovered that another molecule that binds to Lfc called Tctex1 which brings Lfc to the LPA receptor. Once LPA binds to its receptor Lfc is somehow discharged from its inhibitory complex and becomes activated. We will endeavor to discover the mechanism underlying this process. We will analyze the role of Lfc in human tumors by protein expression analysis of primary ovarian tumors. We will remove Lfc from these tumor cells and determine if they can still behave as tumors.

Related projects