Investigating the Roles of Homeobox Proteins and TEAD in Small Cell Lung Cancer

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dc.contributor.authorRicarte, Bea
dc.contributor.supervisorPearson, Joel
dc.date.accessioned2024-07-05T17:42:21Z
dc.date.available2024-07-05T17:42:21Z
dc.date.issued2024-07-05
dc.date.submitted2024-07-05T17:42:21Zen_US
dc.degree.disciplineBiological Sciences
dc.degree.levelBachelor of Science (B.Sc.)
dc.description.abstractLung cancer remains a significant global health concern, responsible for a substantial number of cancer-related deaths annually. Small cell lung cancer (SCLC), one of its subtypes, is particularly aggressive and resistant to treatment, leading to a poor prognosis for patients. Unfortunately, treatment options for SCLC remain limited and have not been advanced for decades. This highlights the urgent need for a deeper understanding of the molecular mechanisms underlying the pathogenesis of SCLC in order to identify novel therapeutic strategies for this disease. DNA-bind proteins, TEADs, play a crucial role in promoting SCLC survival. TEADs are best recognized for their role in interacting with transcriptional activators, YAP and TAZ, however, it was found that the function of TEADs in SCLC is completely independent of YAP and TAZ. Beyond this however, the mechanisms underlying the critical function of TEAD in SCLC is unknown. Preliminary data gathered by the Pearson lab identified the presence of homeobox proteins PROX1, NKX2-1 and NKX2-2 with the TEAD complex in SCLC, prompting the hypothesis that TEAD interacts with these proteins to silence TEAD target genes in SCLC, promoting the cancerous state. Using co-immunoprecipiation, the association of TEAD with PROX1 and NKX2-1 were confirmed. Additionally, CRISPR interference was used to knockdown PROX1, NKX2-1 and NKX2-2 in SCLC cells, to assess their role in TEAD-mediated gene regulation. This resulted in an increase in controlled cell regulation and differentiation genes, and a decrease in SCLC biomarkers, consistent with the hypothesis. However, contrasting the hypothesis, protein knockdowns showed a decrease of cell adhesion genes. Nevertheless, these findings bring light to a novel pathway in SCLC pathogenesis. Understanding the exact mechanisms behind these homeobox proteins and their interaction with TEADs could lead to the development of more effective treatment for SCLC.
dc.identifier.urihttp://hdl.handle.net/1993/38291
dc.language.isoeng
dc.subjectlung cancer
dc.subjectsmall cell lung cancer
dc.subjectTEAD
dc.subjecttherapeutic strategies
dc.subjecthomeobox protiens
dc.titleInvestigating the Roles of Homeobox Proteins and TEAD in Small Cell Lung Cancer
local.author.affiliationFaculty of Science::Department of Biological Sciences
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