{"id":{"repo_id":"buffalo","oai_identifier":"oai:ubir.buffalo.edu:10477/86674"},"canonical_url":"https://search.dev.ndltd.org/etd/buffalo/oai:ubir.buffalo.edu:10477/86674","repository":{"repo_id":"buffalo","name":"Buffalo","base_url":"https://ubir.buffalo.edu/oai/request"},"display":{"title":"Exploring Translation Initiation Dysregulation in Mammary Tumors and Its Effect on Malignancy","abstract":"M.S.","abstract_html":"M.S.","abstract_has_math":false,"creators":["Srinivasan, Aravind; 0000-0002-4424-474X"],"institution":"State University of New York at Buffalo","degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":["Barbi, Joseph","Roswell Park"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2025,"date_issued":"2025-02-21T21:36:19Z","date_published":"2025-02-21T21:36:19Z","updated_at":"2026-07-27T19:05:34Z","subjects":["oncology","biology","immunology"],"languages":["eng"],"rights":["Users of works found in University at Buffalo Institutional Repository (UBIR) are responsible for identifying and contacting the copyright owner for permission to reuse. University at Buffalo Libraries do not manage rights for copyright-protected works and cannot assist with permissions.","Copyright retained by author."],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/10477/86674","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Barbi, Joseph","Roswell Park"]},{"key":"dc:creator","label":"Author","values":["Srinivasan, Aravind; 0000-0002-4424-474X"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2025-02-21T21:36:19Z","2020"]},{"key":"dc:publisher","label":"Institution","values":["State University of New York at Buffalo"]},{"key":"dc:type","label":"Dc Type","values":["Text","Thesis"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["oncology","biology","immunology"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["eng"]},{"key":"dc:rights","label":"Dc Rights","values":["Users of works found in University at Buffalo Institutional Repository (UBIR) are responsible for identifying and contacting the copyright owner for permission to reuse. University at Buffalo Libraries do not manage rights for copyright-protected works and cannot assist with permissions.","Copyright retained by author."]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["http://hdl.handle.net/10477/86674"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["M.S.","Gene expression culminates in protein synthesis and is regulated at a variety of stages: transcriptional, post-transcriptional and translation. In the past decade, there have been many studies demonstrating the mechanisms underlying the control of gene expression at both transcriptional and translational levels. It has been established that abnormal cellular processes like uncontrolled proliferation, altered metabolism, and immune evasion are characteristics of malignancy. Recently, these processes have been linked to translation dysregulation in various cancers and the over-expression of several key factors that drive pro-tumor processes and functions. There are many ways in which protein synthesis mechanisms might be dysregulated: First, the proteins involved in translation initiation may be overexpressed by tumor cells. Second, dysregulation might happen due to increases in the oncogenic signal which negatively impacts the eIF (eukaryotic initiation factor) inhibitors thereby increasing the activity and number of free eIFs in the system which can take part in translation initiation. Third, upregulation of the pathways that activates the eIFs may cause enhanced activation of the free eIFs in the cell this may lead to poor translational control. In the case of Triple negative breast cancer (TNBC), frequently dysregulated pathways include EGFR (epidermal growth factor receptor) and participants in the mTOR axis which converge at the understudied translation initiation factor eIF4B thereby dysregulating its expression and activity. However, the effect and causation of this translation dysregulation is not fully understood. Thus, studying the role of eIF4B dysregulation in survival ad metastasis of TNBC is necessary to create new avenues for targeting and stratification of TNBC. The present study uses two TNBC cell lines with starkly different eIF4B expression levels and shRNA mediated eIF4B knockdown (KD) to study the role played by eIF4B in malignant cells. We documented the effects of eIF4B KD in TNBC using in-vitro assays, and the results revealed the following insights: overexpression of eIF4B may enhance the proliferation of a TNBC tumor cell but does not aid in tumor spread or immune evasion by MDSCs generations and accumulation. Also, eIF4B KD enhanced the expression of PD-L1 on tumor surface, which suggests that eIF4B may adversely affect expression of this immune checkpoint molecule. Our findings may lay the foundation for future work aimed at determining the role of eIF4B in highly metastatic TNBC. They may also help in translation studies relating to new therapeutic target and overcoming drug resistance.","**To request an accessible version of the file(s) associated with this item, contact library@buffalo.edu. Please include the item's persistent URL [http://hdl.handle.net/. . .] in your request.**"]},{"key":"dc:format","label":"Dc Format","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Exploring Translation Initiation Dysregulation in Mammary Tumors and Its Effect on Malignancy"]}]}],"canonical_facts":{"dc:contributor":["Barbi, Joseph","Roswell Park"],"dc:creator":["Srinivasan, Aravind; 0000-0002-4424-474X"],"dc:date":["2025-02-21T21:36:19Z","2020"],"dc:description":["M.S.","Gene expression culminates in protein synthesis and is regulated at a variety of stages: transcriptional, post-transcriptional and translation. In the past decade, there have been many studies demonstrating the mechanisms underlying the control of gene expression at both transcriptional and translational levels. It has been established that abnormal cellular processes like uncontrolled proliferation, altered metabolism, and immune evasion are characteristics of malignancy. Recently, these processes have been linked to translation dysregulation in various cancers and the over-expression of several key factors that drive pro-tumor processes and functions. There are many ways in which protein synthesis mechanisms might be dysregulated: First, the proteins involved in translation initiation may be overexpressed by tumor cells. Second, dysregulation might happen due to increases in the oncogenic signal which negatively impacts the eIF (eukaryotic initiation factor) inhibitors thereby increasing the activity and number of free eIFs in the system which can take part in translation initiation. Third, upregulation of the pathways that activates the eIFs may cause enhanced activation of the free eIFs in the cell this may lead to poor translational control. In the case of Triple negative breast cancer (TNBC), frequently dysregulated pathways include EGFR (epidermal growth factor receptor) and participants in the mTOR axis which converge at the understudied translation initiation factor eIF4B thereby dysregulating its expression and activity. However, the effect and causation of this translation dysregulation is not fully understood. Thus, studying the role of eIF4B dysregulation in survival ad metastasis of TNBC is necessary to create new avenues for targeting and stratification of TNBC. The present study uses two TNBC cell lines with starkly different eIF4B expression levels and shRNA mediated eIF4B knockdown (KD) to study the role played by eIF4B in malignant cells. We documented the effects of eIF4B KD in TNBC using in-vitro assays, and the results revealed the following insights: overexpression of eIF4B may enhance the proliferation of a TNBC tumor cell but does not aid in tumor spread or immune evasion by MDSCs generations and accumulation. Also, eIF4B KD enhanced the expression of PD-L1 on tumor surface, which suggests that eIF4B may adversely affect expression of this immune checkpoint molecule. Our findings may lay the foundation for future work aimed at determining the role of eIF4B in highly metastatic TNBC. They may also help in translation studies relating to new therapeutic target and overcoming drug resistance.","**To request an accessible version of the file(s) associated with this item, contact library@buffalo.edu. Please include the item's persistent URL [http://hdl.handle.net/. . .] in your request.**"],"dc:format":["application/pdf"],"dc:identifier":["http://hdl.handle.net/10477/86674"],"dc:language":["eng"],"dc:publisher":["State University of New York at Buffalo"],"dc:rights":["Users of works found in University at Buffalo Institutional Repository (UBIR) are responsible for identifying and contacting the copyright owner for permission to reuse. University at Buffalo Libraries do not manage rights for copyright-protected works and cannot assist with permissions.","Copyright retained by author."],"dc:subject":["oncology","biology","immunology"],"dc:title":["Exploring Translation Initiation Dysregulation in Mammary Tumors and Its Effect on Malignancy"],"dc:type":["Text","Thesis"]},"updated_at":"2026-07-27T19:05:34Z"}