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The Effects of Nidogen-1 on Claudin-Low Mammary Tumor Cells

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Title: The Effects of Nidogen-1 on Claudin-Low Mammary Tumor Cells
Author: Jagroop, Rebecca
Department: Department of Biomedical Sciences
Program: Biomedical Sciences
Advisor: Moorehead, Roger
Abstract: Nidogen is a glycoprotein that makes up 2-3% of basement membranes and has two isoforms: nidogen-1 (NID1) and nidogen-2 (NID2). There have been limited studies on NID1 and cancer, with results demonstrating decreased invasiveness and metastatic capabilities in Nid1 silenced cells of ovarian cancer and lung metastasis of breast cancer. Through previous work, a murine cell line representative of the claudin-low subtype, known as RJ423, was developed; it demonstrated a 5000-fold increase in Nid1 expression compared to the luminal subtypes. Based on these findings, we hypothesized that a high Nid1 expression contributes to the aggressive, metastatic nature of claudin-low tumors and that a NID1 knockdown would impair tumor proliferation and migration. Through immunofluorescence, migration assays and conditioned media (CM) experiments, it was revealed that a NID1 knockdown does decrease proliferation and migration of claudin low mammary tumor cells. However, NID1 does not impact epithelial to mesenchymal transition (EMT) and the exact effects on downstream effectors remains unclear. These results indicate that NID1 effects are cancer-type dependent and operates through different mechanisms to aid in tumorigenesis and metastasis. Thus, this may provide new therapies to target metastasis in claudin-low breast cancer by targeting NID1.
Date: 2019-08
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