{"id":{"repo_id":"unsw","oai_identifier":"oai:unsworks.library.unsw.edu.au:1959.4/53763"},"canonical_url":"https://search.dev.ndltd.org/etd/unsw/oai:unsworks.library.unsw.edu.au:1959.4/53763","repository":{"repo_id":"unsw","name":"University of New South Wales","base_url":"https://unsworks.unsw.edu.au/oai/provider"},"display":{"title":"The role of Inhibitors of Differentiation proteins ID1 and ID3 in breast cancer metastasis","abstract":"Breast cancer is a leading cause of cancer death in women. While locally-confined breast cancer is generally curable, the survival of patients with metastatic breast cancer is very poor. Treatment for metastatic breast cancer is palliative not curative due to the lack of targeted therapies. Metastasis is a complex process that still remains poorly understood, thus a detailed understanding of the biological complexity that underlies breast cancer metastasis is essential in reducing the lethality of this disease. The Inhibitor of Differentiation proteins 1 and 3 (ID1/3) are transcriptional regulators that control many cell fate and developmental processes and are often deregulated in cancer. Our group and others have previously demonstrated that ID1/3 are required and sufficient for the metastasis of breast cancer in experimental models. However, the mechanisms by which ID1/3 mediate metastasis in breast cancer remain to be determined. Little is known about pathways regulated by ID1/3 in breast cancer as well as their functional role in the multiple steps of metastatic progression. The current body of work was aimed at exploring the role of ID1/3 and their transcriptional targets that mediate their function in breast cancer. This was achieved through the use of a range of in vitro and in vivo techniques to; firstly, examine ID1 expression in a cohort of breast cancer patients. Secondly, a model of inducible, stable Id1/3 knockdown system was employed to establish the function of Id1/3 in the 4T1 breast cancer cell line and to identify Id1/3 target genes. Thirdly, the requirement of Id1/3 in controlling mammary tumour growth and metastasis was determined by conditional knockdown of Id1/3 expression during tumour progression. The data gathered is the first study to identify the global transcriptional targets of Id1/3 in breast cancer as well as to investigate the role of Id1/3 in the multi steps of metastatic cascade. The results presented here showed that ID1 expression is associated with the triple-negative and HER2-enriched subtypes of breast cancer. ID1 expression is enriched in brain metastases compared to patient matched primary breast cancers. Silencing of Id1/3 reduces primary tumour growth and significantly impairs spontaneous lung metastasis. These data strongly suggest Id1/3 as central controllers of the metastatic phenotype in breast cancer. Transcript profiling experiments revealed a multitude of genes that are regulated by Id1/3. Subsequent validation identified several novel Id1/3 target genes and suggested that the function of Id1/3 in 4T1 cells is possibly mediated by Bmi1/Mel18 and TGF-β signalling pathway. Further functional validation is required to confirm this finding.","abstract_html":"Breast cancer is a leading cause of cancer death in women. While locally-confined breast cancer is generally curable, the survival of patients with metastatic breast cancer is very poor. Treatment for metastatic breast cancer is palliative not curative due to the lack of targeted therapies. Metastasis is a complex process that still remains poorly understood, thus a detailed understanding of the biological complexity that underlies breast cancer metastasis is essential in reducing the lethality of this disease. The Inhibitor of Differentiation proteins 1 and 3 (ID1/3) are transcriptional regulators that control many cell fate and developmental processes and are often deregulated in cancer. Our group and others have previously demonstrated that ID1/3 are required and sufficient for the metastasis of breast cancer in experimental models. However, the mechanisms by which ID1/3 mediate metastasis in breast cancer remain to be determined. Little is known about pathways regulated by ID1/3 in breast cancer as well as their functional role in the multiple steps of metastatic progression. The current body of work was aimed at exploring the role of ID1/3 and their transcriptional targets that mediate their function in breast cancer. This was achieved through the use of a range of in vitro and in vivo techniques to; firstly, examine ID1 expression in a cohort of breast cancer patients. Secondly, a model of inducible, stable Id1/3 knockdown system was employed to establish the function of Id1/3 in the 4T1 breast cancer cell line and to identify Id1/3 target genes. Thirdly, the requirement of Id1/3 in controlling mammary tumour growth and metastasis was determined by conditional knockdown of Id1/3 expression during tumour progression. The data gathered is the first study to identify the global transcriptional targets of Id1/3 in breast cancer as well as to investigate the role of Id1/3 in the multi steps of metastatic cascade. The results presented here showed that ID1 expression is associated with the triple-negative and HER2-enriched subtypes of breast cancer. ID1 expression is enriched in brain metastases compared to patient matched primary breast cancers. Silencing of Id1/3 reduces primary tumour growth and significantly impairs spontaneous lung metastasis. These data strongly suggest Id1/3 as central controllers of the metastatic phenotype in breast cancer. Transcript profiling experiments revealed a multitude of genes that are regulated by Id1/3. Subsequent validation identified several novel Id1/3 target genes and suggested that the function of Id1/3 in 4T1 cells is possibly mediated by Bmi1/Mel18 and TGF-β signalling pathway. Further functional validation is required to confirm this finding.","abstract_has_math":false,"creators":["Teo, Wee Siang"],"institution":"UNSW, Sydney","degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2014,"date_issued":"2014","date_published":"2014","updated_at":"2026-07-24T05:33:18Z","subjects":["Inhibitors of Differentiation proteins","Breast Cancer","Metastasis","ID proteins","ID1","ID3"],"languages":["EN"],"rights":["open access","CC BY-NC-ND 3.0","free_to_read"],"rights_urls":["https://purl.org/coar/access_right/c_abf2","https://creativecommons.org/licenses/by-nc-nd/3.0/au/"],"identifier_entries":[{"key":"dc:identifier","label":"Identifier","values":["https://doi.org/10.26190/unsworks/16976"],"render_values":[{"text":"https://doi.org/10.26190/unsworks/16976","href":"https://doi.org/10.26190/unsworks/16976","code":true}]}]},"links":{"outbound_url":"http://hdl.handle.net/1959.4/53763","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:creator","label":"Author","values":["Teo, Wee Siang"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2014"]},{"key":"dc:publisher","label":"Institution","values":["UNSW, Sydney"]},{"key":"dc:type","label":"Dc Type","values":["doctoral thesis","http://purl.org/coar/resource_type/c_db06"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Inhibitors of Differentiation proteins","Breast Cancer","Metastasis","ID proteins","ID1","ID3"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["EN"]},{"key":"dc:rights","label":"Dc Rights","values":["open access","https://purl.org/coar/access_right/c_abf2","CC BY-NC-ND 3.0","https://creativecommons.org/licenses/by-nc-nd/3.0/au/","free_to_read"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["http://hdl.handle.net/1959.4/53763","https://unsworks.unsw.edu.au/bitstreams/a5a56fb9-dfe2-4e3e-a88c-d32243ca8471/download","https://doi.org/10.26190/unsworks/16976"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["Breast cancer is a leading cause of cancer death in women. While locally-confined breast cancer is generally curable, the survival of patients with metastatic breast cancer is very poor. Treatment for metastatic breast cancer is palliative not curative due to the lack of targeted therapies. Metastasis is a complex process that still remains poorly understood, thus a detailed understanding of the biological complexity that underlies breast cancer metastasis is essential in reducing the lethality of this disease. The Inhibitor of Differentiation proteins 1 and 3 (ID1/3) are transcriptional regulators that control many cell fate and developmental processes and are often deregulated in cancer. Our group and others have previously demonstrated that ID1/3 are required and sufficient for the metastasis of breast cancer in experimental models. However, the mechanisms by which ID1/3 mediate metastasis in breast cancer remain to be determined. Little is known about pathways regulated by ID1/3 in breast cancer as well as their functional role in the multiple steps of metastatic progression. The current body of work was aimed at exploring the role of ID1/3 and their transcriptional targets that mediate their function in breast cancer. This was achieved through the use of a range of in vitro and in vivo techniques to; firstly, examine ID1 expression in a cohort of breast cancer patients. Secondly, a model of inducible, stable Id1/3 knockdown system was employed to establish the function of Id1/3 in the 4T1 breast cancer cell line and to identify Id1/3 target genes. Thirdly, the requirement of Id1/3 in controlling mammary tumour growth and metastasis was determined by conditional knockdown of Id1/3 expression during tumour progression. The data gathered is the first study to identify the global transcriptional targets of Id1/3 in breast cancer as well as to investigate the role of Id1/3 in the multi steps of metastatic cascade. The results presented here showed that ID1 expression is associated with the triple-negative and HER2-enriched subtypes of breast cancer. ID1 expression is enriched in brain metastases compared to patient matched primary breast cancers. Silencing of Id1/3 reduces primary tumour growth and significantly impairs spontaneous lung metastasis. These data strongly suggest Id1/3 as central controllers of the metastatic phenotype in breast cancer. Transcript profiling experiments revealed a multitude of genes that are regulated by Id1/3. Subsequent validation identified several novel Id1/3 target genes and suggested that the function of Id1/3 in 4T1 cells is possibly mediated by Bmi1/Mel18 and TGF-β signalling pathway. Further functional validation is required to confirm this finding."]},{"key":"dc:format","label":"Dc Format","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["The role of Inhibitors of Differentiation proteins ID1 and ID3 in breast cancer metastasis"]}]}],"canonical_facts":{"dc:creator":["Teo, Wee Siang"],"dc:date":["2014"],"dc:description":["Breast cancer is a leading cause of cancer death in women. While locally-confined breast cancer is generally curable, the survival of patients with metastatic breast cancer is very poor. Treatment for metastatic breast cancer is palliative not curative due to the lack of targeted therapies. Metastasis is a complex process that still remains poorly understood, thus a detailed understanding of the biological complexity that underlies breast cancer metastasis is essential in reducing the lethality of this disease. The Inhibitor of Differentiation proteins 1 and 3 (ID1/3) are transcriptional regulators that control many cell fate and developmental processes and are often deregulated in cancer. Our group and others have previously demonstrated that ID1/3 are required and sufficient for the metastasis of breast cancer in experimental models. However, the mechanisms by which ID1/3 mediate metastasis in breast cancer remain to be determined. Little is known about pathways regulated by ID1/3 in breast cancer as well as their functional role in the multiple steps of metastatic progression. The current body of work was aimed at exploring the role of ID1/3 and their transcriptional targets that mediate their function in breast cancer. This was achieved through the use of a range of in vitro and in vivo techniques to; firstly, examine ID1 expression in a cohort of breast cancer patients. Secondly, a model of inducible, stable Id1/3 knockdown system was employed to establish the function of Id1/3 in the 4T1 breast cancer cell line and to identify Id1/3 target genes. Thirdly, the requirement of Id1/3 in controlling mammary tumour growth and metastasis was determined by conditional knockdown of Id1/3 expression during tumour progression. The data gathered is the first study to identify the global transcriptional targets of Id1/3 in breast cancer as well as to investigate the role of Id1/3 in the multi steps of metastatic cascade. The results presented here showed that ID1 expression is associated with the triple-negative and HER2-enriched subtypes of breast cancer. ID1 expression is enriched in brain metastases compared to patient matched primary breast cancers. Silencing of Id1/3 reduces primary tumour growth and significantly impairs spontaneous lung metastasis. These data strongly suggest Id1/3 as central controllers of the metastatic phenotype in breast cancer. Transcript profiling experiments revealed a multitude of genes that are regulated by Id1/3. Subsequent validation identified several novel Id1/3 target genes and suggested that the function of Id1/3 in 4T1 cells is possibly mediated by Bmi1/Mel18 and TGF-β signalling pathway. Further functional validation is required to confirm this finding."],"dc:format":["application/pdf"],"dc:identifier":["http://hdl.handle.net/1959.4/53763","https://unsworks.unsw.edu.au/bitstreams/a5a56fb9-dfe2-4e3e-a88c-d32243ca8471/download","https://doi.org/10.26190/unsworks/16976"],"dc:language":["EN"],"dc:publisher":["UNSW, Sydney"],"dc:rights":["open access","https://purl.org/coar/access_right/c_abf2","CC BY-NC-ND 3.0","https://creativecommons.org/licenses/by-nc-nd/3.0/au/","free_to_read"],"dc:subject":["Inhibitors of Differentiation proteins","Breast Cancer","Metastasis","ID proteins","ID1","ID3"],"dc:title":["The role of Inhibitors of Differentiation proteins ID1 and ID3 in breast cancer metastasis"],"dc:type":["doctoral thesis","http://purl.org/coar/resource_type/c_db06"]},"updated_at":"2026-07-24T05:33:18Z"}