Author ORCID Identifier
Date of Graduation
8-2019
Document Type
Thesis (MS)
Program Affiliation
Cancer Biology
Degree Name
Masters of Science (MS)
Advisor/Committee Chair
Giulio F. Draetta
Committee Member
Swathi Arur
Committee Member
Richard Behringer
Committee Member
George T. Eisenhoffer
Committee Member
Haoqiang Ying
Abstract
Pancreatic Ductal Adenocarcinoma (PDAC) is the 3rd leading cause of cancer death in the US. We performed loss of function genomic screening on a cohort of four patient derived PDAC cell populations and our data shows a cell surface receptor CD109 to be a common vulnerability, the biologic role of which in PDAC is yet unstudied and largely unknown. We hypothesized that CD109 expression provides PDAC cells with a survival advantage, and promotes cancer progression through activation of downstream signaling. We believe therefore that targeting CD109 could improve PDAC patients’ survival. Here we report that CD109 plays a role in cell proliferation, viability, and clonogenicity in vitro. We also find that it promotes tumor formation and progression in nude mice, therefore decreasing their survival. We revealed an association between CD109 expression and YAP/TAZ signaling through RPPA and RNA Sequencing data. This data establishes CD109 as a cell surface protein exclusively expressed in PDAC rather than healthy pancreatic tissue, demonstrating pro-oncogenic behavior and tumor initiation potential in vitro and in vivo. This helps us understand more about PDAC and provides insights into a relatively unknown protein with a therapeutic potential.
Keywords
CD109, PDAC, cancer, pancreas, functional genomics
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