Names: Thomas Luh and Joy Jin High Schools: Leland High School and Gunn High School

1. Names: Thomas Luh and Joy Jin High Schools: Leland High School and Gunn High School Mentor: Dr. Hui Li Project Title: Hedgehog-Gli Signaling Promotes Cell Proliferation and Epithelial-to-Mesenchymal Transition in Lung Cancer Lung cancer is the leading cause of cancer death in the United States. A majority of cancer patients are diagnosed with metastatic phenotypes. It remains a scientific challenge to develop novel therapeutic strategies based on molecular mechanisms of cancer and metastatic process. Epithelial-to-Mesenchymal Transition (EMT), characterized by loss of epithelial markers, such as E-cadherin, is involved in the metastatic process. Aberrant activation of the Hedgehog-Gli signaling pathway is implicated in various cancers, including lung cancer. EMT regulation through the Hh pathway has emerged in literature, but data remains controversial. We hypothesize that SHh signaling activates the downstream Gli family of proteins, which promotes cell proliferation and EMT, leading to lung cancer cell invasion and metastasis. Our results demonstrated elevated Gli expression in tumors, and suggested inverse correlations between Gli and E-cadherin levels through immunohistochemistry, immunofluencesent stainings, western blot and quantitative RT-PCR. Results indicated that elevated suppression of Gli by an inhibitor reduced tumor cell regeneration, with Hh/Gli signaling promoting cell migration through downregulation of E-Cad in a wound healing assay. Expression analyses were conducted at both protein and RNA levels. Our findings strongly suggest Hedgehog-Gli roles in promoting cell proliferation and EMT in lung cancer.