Implications of TGFβ Signaling and CDK Inhibition for the Treatment of Breast Cancer

TGFβ signaling enacts tumor-suppressive functions in normal cells through promotion of several cell regulatory actions including cell-cycle control and apoptosis. Canonical TGFβ signaling proceeds through phosphorylation of the transcription factor, SMAD3, at the C-terminus of the protein. During on...

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Autores principales:	Joseph T. Decker, Jeffrey A. Ma, Lonnie D. Shea, Jacqueline S. Jeruss
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	breast cancer CDK inhibitor TGFβ SMAD3 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/201ed25b35bb465cbe9f3da4b58fbc5f
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spelling	oai:doaj.org-article:201ed25b35bb465cbe9f3da4b58fbc5f2021-11-11T15:28:46ZImplications of TGFβ Signaling and CDK Inhibition for the Treatment of Breast Cancer10.3390/cancers132153432072-6694https://doaj.org/article/201ed25b35bb465cbe9f3da4b58fbc5f2021-10-01T00:00:00Zhttps://www.mdpi.com/2072-6694/13/21/5343https://doaj.org/toc/2072-6694TGFβ signaling enacts tumor-suppressive functions in normal cells through promotion of several cell regulatory actions including cell-cycle control and apoptosis. Canonical TGFβ signaling proceeds through phosphorylation of the transcription factor, SMAD3, at the C-terminus of the protein. During oncogenic progression, this tumor suppressant phosphorylation of SMAD3 can be inhibited. Overexpression of cyclins D and E, and subsequent hyperactivation of cyclin-dependent kinases 2/4 (CDKs), are often observed in breast cancer, and have been associated with poor prognosis. The noncanonical phosphorylation of SMAD3 by CDKs 2 and 4 leads to the inhibition of tumor-suppressive function of SMAD3. As a result, CDK overactivation drives oncogenic progression, and can be targeted to improve clinical outcomes. This review focuses on breast cancer, and highlights advances in the understanding of CDK-mediated noncanonical SMAD3 phosphorylation. Specifically, the role of aberrant TGFβ signaling in oncogenic progression and treatment response will be examined to illustrate the potential for therapeutic discovery in the context of cyclins/CDKs and SMAD3.Joseph T. DeckerJeffrey A. MaLonnie D. SheaJacqueline S. JerussMDPI AGarticlebreast cancerCDK inhibitorTGFβSMAD3Neoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENCancers, Vol 13, Iss 5343, p 5343 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	breast cancer CDK inhibitor TGFβ SMAD3 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	breast cancer CDK inhibitor TGFβ SMAD3 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Joseph T. Decker Jeffrey A. Ma Lonnie D. Shea Jacqueline S. Jeruss Implications of TGFβ Signaling and CDK Inhibition for the Treatment of Breast Cancer
description	TGFβ signaling enacts tumor-suppressive functions in normal cells through promotion of several cell regulatory actions including cell-cycle control and apoptosis. Canonical TGFβ signaling proceeds through phosphorylation of the transcription factor, SMAD3, at the C-terminus of the protein. During oncogenic progression, this tumor suppressant phosphorylation of SMAD3 can be inhibited. Overexpression of cyclins D and E, and subsequent hyperactivation of cyclin-dependent kinases 2/4 (CDKs), are often observed in breast cancer, and have been associated with poor prognosis. The noncanonical phosphorylation of SMAD3 by CDKs 2 and 4 leads to the inhibition of tumor-suppressive function of SMAD3. As a result, CDK overactivation drives oncogenic progression, and can be targeted to improve clinical outcomes. This review focuses on breast cancer, and highlights advances in the understanding of CDK-mediated noncanonical SMAD3 phosphorylation. Specifically, the role of aberrant TGFβ signaling in oncogenic progression and treatment response will be examined to illustrate the potential for therapeutic discovery in the context of cyclins/CDKs and SMAD3.
format	article
author	Joseph T. Decker Jeffrey A. Ma Lonnie D. Shea Jacqueline S. Jeruss
author_facet	Joseph T. Decker Jeffrey A. Ma Lonnie D. Shea Jacqueline S. Jeruss
author_sort	Joseph T. Decker
title	Implications of TGFβ Signaling and CDK Inhibition for the Treatment of Breast Cancer
title_short	Implications of TGFβ Signaling and CDK Inhibition for the Treatment of Breast Cancer
title_full	Implications of TGFβ Signaling and CDK Inhibition for the Treatment of Breast Cancer
title_fullStr	Implications of TGFβ Signaling and CDK Inhibition for the Treatment of Breast Cancer
title_full_unstemmed	Implications of TGFβ Signaling and CDK Inhibition for the Treatment of Breast Cancer
title_sort	implications of tgfβ signaling and cdk inhibition for the treatment of breast cancer
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/201ed25b35bb465cbe9f3da4b58fbc5f
work_keys_str_mv	AT josephtdecker implicationsoftgfbsignalingandcdkinhibitionforthetreatmentofbreastcancer AT jeffreyama implicationsoftgfbsignalingandcdkinhibitionforthetreatmentofbreastcancer AT lonniedshea implicationsoftgfbsignalingandcdkinhibitionforthetreatmentofbreastcancer AT jacquelinesjeruss implicationsoftgfbsignalingandcdkinhibitionforthetreatmentofbreastcancer
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Implications of TGFβ Signaling and CDK Inhibition for the Treatment of Breast Cancer

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