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Full-Text Articles in Life Sciences

4d Ex Vivo Crispr/Cas9 Whole-Genome Screen To Identify Genes Regulating Lung Cancer Metastasis, Alexandria Plumer Dec 2021

4d Ex Vivo Crispr/Cas9 Whole-Genome Screen To Identify Genes Regulating Lung Cancer Metastasis, Alexandria Plumer

Dissertations & Theses (Open Access)

Metastatic lung cancer has a 5-year survival rate of 5%. Lung cancers tend to be asymptomatic until late stages, and almost 90% are not diagnosed until they are advanced. Metastases are very rare events, often initiated by a single cell from a primary tumor into a new niche at a distant location. Investigation of the early metastatic process is of urgent need for the development of early diagnostics and targeted therapeutics. We performed a proof-of-concept CRISPR/Cas9 whole genome knockout screen in the A549 lung adenocarcinoma cell line and utilized a novel ex vivo 4D lung metastasis model to find gene …


Molecular Mechanism Of Action Of The Natural Polyphenolic Compound And The P300 Inhibitor “Carnosol” Against The Triple Negative Breast Cance, Halima Ali Mohammed Salem Alsamri Nov 2021

Molecular Mechanism Of Action Of The Natural Polyphenolic Compound And The P300 Inhibitor “Carnosol” Against The Triple Negative Breast Cance, Halima Ali Mohammed Salem Alsamri

Dissertations

Carnosol, a naturally occurring Phyto polyphenol found in sage, oregano, and rosemary, has been extensively studied by our laboratory for its anticancer effects in various types of cancer. In human Triple-Negative Breast Cancer (TNBC), carnosol was shown to inhibit cellular viability, colony growth, induced cell cycle arrest, autophagy, and apoptosis. Nonetheless, very little is known about the molecular mechanism of action. In the current study, the ability of carnosol to inhibit metastasis and tumour growth was examined. Wound healing and invasion assays revealed that carnosol inhibited migration and invasion at non-cytotoxic concentrations of MDA-MB-231 cells. Also, carnosol was found to …


Understanding The Mechanistic Roles Of Integrin Alpha 6 In Tumor Development Using A Humanized Zebrafish (Danio Rerio) Model System, Ashley B. Williams Aug 2021

Understanding The Mechanistic Roles Of Integrin Alpha 6 In Tumor Development Using A Humanized Zebrafish (Danio Rerio) Model System, Ashley B. Williams

Honors College Theses

Present day cancer incidence and mortality rates indicate the need for effective cancer diagnostic tools and targeted cancer therapeutic strategies. Recent studies have focused on the biological pathways of cells and tumor microenvironments to identify putative biomarkers and potential drug targets as diagnostic and therapeutic tools. Human integrins, adhesion receptors, have become the focal points in these studies, specifically Integrin Alpha 6 (ITGA6) which has been implicated in major tumor progression roles: metastasis and angiogenesis. These characteristics make ITGA6 an excellent candidate for potential drug or diagnostic target, however, the mechanism by which ITGA6 facilitates tumor progression remains unclear. Cell …


Investigation Of Β5 Integrin Function In Epithelial Ovarian Cancer Cell Adhesion And Metastatic Properties Of Spheroids, Dolly Dhaliwal Aug 2021

Investigation Of Β5 Integrin Function In Epithelial Ovarian Cancer Cell Adhesion And Metastatic Properties Of Spheroids, Dolly Dhaliwal

Electronic Thesis and Dissertation Repository

Epithelial ovarian cancer (EOC) is the most lethal gynaecological malignancy in the developed world. EOC metastasis is unique since malignant cells detach directly from the primary tumor site into the abdominal fluid and form multicellular aggregates, called spheroids, that possess enhanced survival mechanisms while in suspension. As such, altered cell adhesion properties are paramount to EOC metastasis with cell detachment from the primary tumor, dissemination as spheroids, and reattachment to peritoneal surfaces for secondary tumor formation. These interactions play a crucial role in cell-cell and cell-extracellular matrix interactions, having implications in multiple steps of cancer progression. We previously showed that …


Examining The Mechanistic Roles Of Integrin Alpha-6 In Cancer Metastasis., Chase T. Clark Mar 2021

Examining The Mechanistic Roles Of Integrin Alpha-6 In Cancer Metastasis., Chase T. Clark

Honors College Theses

Metastasis- the spread of cancer cells from the primary tumor to the surrounding tissues- is responsible for 90% of cancer deaths. Integrin alpha-6 (ITGA6) is a specific transmembrane cell surface protein that functions in cell surface adhesion and signaling. ITGA6 is upregulated in many types of cancers and promotes the migration and invasion of cancer cells to surrounding tissues. It is my objective to determine the mechanism through which ITGA6 facilitates the migration of cancer cells through the extracellular matrix (ECM). These experiments helped to establish the role of ITGA6 in tumor development and provide focus for possible chemotherapeutic treatment. …


Functional Role Of Dream And Dyrk1a In High-Grade Serous Ovarian Cancer Cell Dormancy, Pirunthan Perampalam Mar 2021

Functional Role Of Dream And Dyrk1a In High-Grade Serous Ovarian Cancer Cell Dormancy, Pirunthan Perampalam

Electronic Thesis and Dissertation Repository

High-grade serous ovarian cancer (HGSOC) is the most common form of ovarian cancer. The majority of women are disproportionately diagnosed at an advanced stage (stage III-IV) of the disease when tumours have progressed beyond the ovaries or fallopian tubes and into the peritoneal cavity. Survival rates at late-stage are as low as 25% and chemoresistant disease recurrence is common, affecting up to 90% of patients. Multicellular clusters called spheroids contribute to dormancy, chemoresistance, and metastases and are a major challenge to treatment of HGSOC. Spheroid cells undergo reversible quiescence to evade chemotherapy in a process mediated by the mammalian DREAM …


Long Noncoding Rna Ak001796 As A Mediator Of Epithelial-To-Mesenchymal Transition In Metastatic Breast Cancer, Sumayya Adib Alchalabi Jan 2021

Long Noncoding Rna Ak001796 As A Mediator Of Epithelial-To-Mesenchymal Transition In Metastatic Breast Cancer, Sumayya Adib Alchalabi

Legacy Theses & Dissertations (2009 - 2024)

Long noncoding RNAs (lncRNAs) are emerging as key molecules regulating several cellular pathways and contributing to the development and progression of different diseases including cancer. The epithelial-to- mesenchymal transition (EMT), a molecular reprogramming process that plays a critical role in cancer metastasis, involves a complex interaction between protein coding and non-coding transcripts including lncRNAs. Understanding the biological significance of those lncRNAs of relatively unknown function, may help to uncover potential therapeutic targets for the aggressive subtypes of breast and other cancers. In this study, we examined the expression profiles of more than 17,000 lncRNAs in a large set of patients’ …


Nuclear Aurora-A Kinase-Induced Hypoxia Signaling Drives Dissemination And Metastasis In Breast Cancer., Kristina Marinak Whately Jan 2021

Nuclear Aurora-A Kinase-Induced Hypoxia Signaling Drives Dissemination And Metastasis In Breast Cancer., Kristina Marinak Whately

Graduate Theses, Dissertations, and Problem Reports

Metastatic breast cancer causes the vast majority of cancer-associated deaths, especially in triple negative breast cancers (TNBC). TNBC is still poorly understood and has no effective treatment. Here we reveal that presence of Aurora-A Kinase (AURKA) in the nucleus and metastatic dissemination are molecularly connected through HIF1 (Hypoxia induced factor-1) signaling. The nuclear AURKA in the complex with constitutively expressed HIF-1β subunit activates transcription of “hypoxia induced genes” under normoxic conditions (the phenomenon called pseudohypoxia) without upregulation of oxygen-sensitive HIF-1α subunit. We uncover that AURKA preferentially binds to and phosphorylates HIF-1β, and co-localizes with HIF complex on DNA. The mass …