Low lamin A levels enhance confined cell migration and metastatic capacity in breast cancer
Autor: | Emily S. Bell, Pragya Shah, Noam Zuela-Sopilniak, Dongsung Kim, Alice-Anais Varlet, Julien L.P. Morival, Alexandra L. McGregor, Philipp Isermann, Patricia M. Davidson, Joshua J. Elacqua, Jonathan N. Lakins, Linda Vahdat, Valerie M. Weaver, Marcus B. Smolka, Paul N. Span, Jan Lammerding |
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Rok vydání: | 2022 |
Předmět: |
Cancer Research
Cell Breast Neoplasms Biology medicine.disease_cause Article Metastasis Phosphatidylinositol 3-Kinases Breast cancer Downregulation and upregulation Cell Movement medicine Genetics Humans Molecular Biology Women's cancers Radboud Institute for Molecular Life Sciences [Radboudumc 17] Cancer Cell migration Lamin Type A medicine.disease medicine.anatomical_structure Cancer research Female Carcinogenesis Proto-Oncogene Proteins c-akt Lamin |
Zdroj: | Oncogene, 41, 4211-4230 Oncogene, 41, 36, pp. 4211-4230 Oncogene |
ISSN: | 1476-5594 0950-9232 |
Popis: | Contains fulltext : 283431.pdf (Publisher’s version ) (Closed access) Aberrations in nuclear size and shape are commonly used to identify cancerous tissue. However, it remains unclear whether the disturbed nuclear structure directly contributes to the cancer pathology or is merely a consequence of other events occurring during tumorigenesis. Here, we show that highly invasive and proliferative breast cancer cells frequently exhibit Akt-driven lower expression of the nuclear envelope proteins lamin A/C, leading to increased nuclear deformability that permits enhanced cell migration through confined environments that mimic interstitial spaces encountered during metastasis. Importantly, increasing lamin A/C expression in highly invasive breast cancer cells reflected gene expression changes characteristic of human breast tumors with higher LMNA expression, and specifically affected pathways related to cell-ECM interactions, cell metabolism, and PI3K/Akt signaling. Further supporting an important role of lamins in breast cancer metastasis, analysis of lamin levels in human breast tumors revealed a significant association between lower lamin A levels, Akt signaling, and decreased disease-free survival. These findings suggest that downregulation of lamin A/C in breast cancer cells may influence both cellular physical properties and biochemical signaling to promote metastatic progression. |
Databáze: | OpenAIRE |
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