The expression and role of the Lem-D proteins Ankle2, Emerin, Lemd2, and TMPO in triple-negative breast cancer cell growth.

Autor:	Rose M; Cancer and Ageing Research Program, Centre for Genomics and Personalised Health, School of Biomedical Sciences, Translational Research Institute, Queensland University of Technology, Brisbane, QLD, Australia., Burgess JT; Cancer and Ageing Research Program, Centre for Genomics and Personalised Health, School of Biomedical Sciences, Translational Research Institute, Queensland University of Technology, Brisbane, QLD, Australia., Cheong CM; Cancer and Ageing Research Program, Centre for Genomics and Personalised Health, School of Biomedical Sciences, Translational Research Institute, Queensland University of Technology, Brisbane, QLD, Australia., Adams MN; Cancer and Ageing Research Program, Centre for Genomics and Personalised Health, School of Biomedical Sciences, Translational Research Institute, Queensland University of Technology, Brisbane, QLD, Australia., Shahrouzi P; Department of Medical Genetics, Faculty of Medicine, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway., O'Byrne KJ; Cancer and Ageing Research Program, Centre for Genomics and Personalised Health, School of Biomedical Sciences, Translational Research Institute, Queensland University of Technology, Brisbane, QLD, Australia.; Cancer Services, Princess Alexandra Hospital, Brisbane, QLD, Australia., Richard DJ; Cancer and Ageing Research Program, Centre for Genomics and Personalised Health, School of Biomedical Sciences, Translational Research Institute, Queensland University of Technology, Brisbane, QLD, Australia., Bolderson E; Cancer and Ageing Research Program, Centre for Genomics and Personalised Health, School of Biomedical Sciences, Translational Research Institute, Queensland University of Technology, Brisbane, QLD, Australia.
Jazyk:	angličtina
Zdroj:	Frontiers in oncology [Front Oncol] 2024 Apr 24; Vol. 14, pp. 1222698. Date of Electronic Publication: 2024 Apr 24 (Print Publication: 2024).
DOI:	10.3389/fonc.2024.1222698
Abstrakt:	Background: Triple-negative breast cancer (TNBC) is a sub-classification of breast carcinomas, which leads to poor survival outcomes for patients. TNBCs do not possess the hormone receptors that are frequently targeted as a therapeutic in other cancer subtypes and, therefore, chemotherapy remains the standard treatment for TNBC. Nuclear envelope proteins are frequently dysregulated in cancer cells, supporting their potential as novel cancer therapy targets. The Lem-domain (Lem-D) (LAP2, Emerin, MAN1 domain, and Lem-D) proteins are a family of inner nuclear membrane proteins, which share a ~45-residue Lem-D. The Lem-D proteins, including Ankle2, Lemd2, TMPO, and Emerin, have been shown to be associated with many of the hallmarks of cancer. This study aimed to define the association between the Lem-D proteins and TNBC and determine whether these proteins could be promising therapeutic targets. Methods: GENT2, TCGA, and KM plotter were utilized to investigate the expression and prognostic implications of several Lem-D proteins: Ankle2, TMPO, Emerin, and Lemd2 in publicly available breast cancer patient data. Immunoblotting and immunofluorescent analysis of immortalized non-cancerous breast cells and a panel of TNBC cells were utilized to establish whether protein expression of the Lem-D proteins was significantly altered in TNBC. SiRNA was used to decrease individual Lem-D protein expression, and functional assays, including proliferation assays and apoptosis assays, were conducted. Results: The Lem-D proteins were generally overexpressed in TNBC patient samples at the mRNA level and showed variable expression at the protein level in TNBC cell lysates. Similarly, protein levels were generally negatively correlated with patient survival outcomes. siRNA-mediated depletion of the individual Lem-D proteins in TNBC cells induced aberrant nuclear morphology, decreased proliferation, and induced cell death. However, minimal effects on nuclear morphology or cell viability were observed following Lem-D depletion in non-cancerous MCF10A cells. Conclusion: There is evidence to suggest that Ankle2, TMPO, Emerin, and Lemd2 expressions are correlated with breast cancer patient outcomes, but larger patient sample numbers are required to confirm this. siRNA-mediated depletion of these proteins was shown to specifically impair TNBC cell growth, suggesting that the Lem-D proteins may be a specific anti-cancer target. Competing Interests: Authors EB, DR, and KO are founders of Carpe Vitae Pharmaceuticals. EB, KO, and DR are inventors on provisional patent applications filed by Queensland University of Technology. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2024 Rose, Burgess, Cheong, Adams, Shahrouzi, O’Byrne, Richard and Bolderson.)
Databáze:	MEDLINE
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