Roles of ADAM12 in triple-negative breast cancer: regulation of cancer stem cells

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Show simple item record Qi, Yue 2017-07-10T20:08:40Z 2017-07-10T20:08:40Z 2016-05-01 en_US
dc.description.abstract ADAM12 (A Disintegrin and Metalloprotease 12) is a cell surface protease, which is deregulated in many human diseases. High expression of ADAM12 in triple-negative breast cancers (lacking estrogen receptor, progesterone receptor, and HER2 expression) is associated with poor patient prognosis. My dissertation focused on the understanding of the biological functions of ADAM12 in triple-negative breast cancers. I found that ADAM12 is significantly upregulated in the claudin-low molecular subtype of breast cancer. Claudin-low tumors are typically triple-negative and are enriched in cancer stem cells. Here, I demonstrated that the loss of ADAM12 expression not only decreased the number of cancer stem-like cells in vitro but also significantly compromised the tumor-initiating capabilities of breast cancer cells in vivo. This is the first evidence showing that ADAM12 might regulate the cancer stem cell-like phenotype in triple-negative breast cancers. I also discovered a novel mechanism of ADAM12-regulated signaling by transforming growth factor β (TGFβ) through modulation of TGFBR1 mRNA expression in breast cancer cells. Lastly, I characterized the effects of six different somatic mutations in the ADAM12 gene found in human breast cancers on the intracellular trafficking, post-translational processing, and function of ADAM12 protein. Collectively, the findings of this study support the notion that ADAM12 with catalytically active metalloprotease domain is required for the progression of triple-negative breast cancers. en_US
dc.language.iso en_US en_US
dc.publisher Kansas State University en
dc.subject Breast cancer en_US
dc.subject Cell signaling en_US
dc.subject Protein chemistry en_US
dc.subject Stem cells en_US
dc.subject Genetic mutations en_US
dc.subject Membrane receptors en_US
dc.title Roles of ADAM12 in triple-negative breast cancer: regulation of cancer stem cells en_US
dc.type Dissertation en_US Doctor of Philosophy en_US
dc.description.level Doctoral en_US
dc.description.department Biochemistry and Molecular Biophysics Interdepartmental Program en_US
dc.description.advisor Anna Zolkiewska en_US 2016 en_US May en_US

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