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

Sep 21, 2026

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Triple-negative breast cancer (TNBC) lacks hormone receptors and relies primarily on chemotherapy, while nuclear envelope proteins are often dysregulated and may provide novel therapeutic targets. This study examined how Lem-domain (LemD) proteins—Ankle2, Emerin, Lemd2, and TMPO—relate to TNBC biology and patient outcomes. Public transcriptomic datasets were analyzed for expression and prognostic associations, and protein changes were tested using immunoblotting and immunofluorescence. Functional studies with siRNA assessed effects on nuclear morphology, proliferation, and apoptosis in TNBC versus noncancerous cells.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages14

Reading Time35 min

AccessFree to download

Background

Methods

Results

Conclusion

Introduction

Nuclear envelope context

TYPE Original Research PUBLISHED 24 April 2024 DOI 10.3389/fonc.2024.1222698 OPEN ACCESS EDITED BY Anika Nagelkerke, University of Groningen, Netherlands REVIEWED BY Xiaohui Liu, Dalian Medical University, China Francesco Salvatore, University of Naples Federico II, Italy *CORRESPONDENCE Emma Bolderson [emma.bolderson@qut.edu.au](emma.bolderson@qut.edu.au) RECEIVED 15 May 2023 ACCEPTED 28 February 2024 PUBLISHED 24 April 2024 CITATION Rose M, Burgess JT, Cheong CM, Adams MN, Shahrouzi P, O ’ Byrne KJ, Richard DJ and Bolderson E (2024) The expression and role of the Lem-D proteins Ankle2, Emerin, Lemd2, and TMPO in triple-negative breast cancer cell growth. Front. Oncol. 14:1222698 . doi: 10.3389/fonc.2024.1222698 COPYRIGHT © 2024 Rose, Burgess, Cheong, Adams, Shahrouzi, O’ Byrne, Richard and Bolderson. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. The expression and role of the Lem-D proteins Ankle2, Emerin, Lemd2, and TMPO in triple-negative breast cancer cell growth Maddison Rose 1, Joshua T. Burgess 1, Chee Man Cheong 1, Mark N. Adams 1, Parastoo Shahrouzi 2, Kenneth J. O’ Byrne 1,3, Derek J. Richard 1 and Emma Bolderson 1* 1Cancer and Ageing Research Program, Centre for Genomics and Personalised Health, School of Biomedical Sciences, Translational Research Institute, Queensland University of Technology, Brisbane, QLD, Australia, 2 Department of Medical Genetics, Faculty of Medicine, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway, 3Cancer Services, Princess Alexandra Hospital, Brisbane, QLD, Australia 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 (LemD) (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 noncancerous 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 LemD proteins in TNBC cells induced aberrant nuclear morphology, decreased proliferation, and induced cell death. However, minimal effects on nuclear morphology or cell viability

FAQs

What was the main goal of the study on Lem-D proteins in TNBC?

To define the association between Lem-D proteins (Ankle2, Emerin, Lemd2, TMPO) and triple-negative breast cancer, and to evaluate whether these proteins could be promising therapeutic targets.

How were expression patterns of Lem-D proteins assessed in TNBC?

The study used publicly available patient data tools to examine expression and prognostic implications, and it used immunoblotting and immunofluorescent analysis to determine whether protein expression differed between TNBC cells and noncancerous breast cells.

What effects did siRNA depletion of Lem-D proteins have on TNBC cells?

siRNA-mediated depletion induced aberrant nuclear morphology, decreased proliferation, and induced cell death in TNBC cells, while showing minimal effects on nuclear morphology or viability in noncancerous MCF10A cells.

Sep 21, 2026

Uploaded by Aurora