Emerin deficiency drives MCF7 cells to an invasive phenotype

Sep 21, 2026

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Emerin deficiency increases nuclear malleability and promotes invasive behavior in MCF7 breast cancer cells during metastasis. The study links reduced emerin protein to smaller, misshapen nuclei and altered nuclear compliance, leading to higher metastasis rates versus non-cancerous controls. Downregulating emerin in noninvasive MCF7 cells impairs migration control, while invasive breast cancer models show comparable effects. Analysis of 192 patient samples finds emerin expression inversely correlates with cancer invasiveness, supporting emerin loss as a driver of invasive transformation and a potential biomarker.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages15

Reading Time38 min

AccessFree to download

Background

Metastasis and nuclear mechanics

Nuclear morphology as a diagnostic signal

Role of emerin

Nucleoskeletal regulation

Prior findings in breast cancer models

Evidence across cancers and clinical relevance

Prostate, hepatocellular, lung, and ovarian cancers

Epithelial-to-mesenchymal transition

Patient sample correlation

[www. nature.com/scientificreports](www. nature.com/scientificreports) OPEN Emerin deficiency drives MCF7 cells to an invasive phenotype Emily Hansen1,2, Christal Rolling1,2, Matthew Wang1,3 & James M. Holaska1,2* During metastasis, cancer cells traverse the vasculature by squeezing through very small gaps in the endothelium. Thus, nuclei in metastatic cancer cells must become more malleable to move through these gaps. Our lab showed invasive breast cancer cells have 50% less emerin protein resulting in smaller, misshapen nuclei, and higher metastasis rates than non-cancerous controls. Thus, emerin deficiency was predicted to cause increased nuclear compliance, cell migration, and metastasis. We tested this hypothesis by downregulating emerin in noninvasive MCF7 cells and found emerin knockdown causes smaller, dysmorphic nuclei, resulting in increased impeded cell migration. Emerin reduction in invasive breast cancer cells showed similar results. Supporting the clinical relevance of emerin reduction in cancer progression, our analysis of 192 breast cancer patient samples showed emerin expression inversely correlates with cancer invasiveness. We conclude emerin loss is an important driver of invasive transformation and has utility as a biomarker for tumor progression. Keywords Emerin, Nucleoskeleton, Metastasis, Breast cancer Breast cancer metastasis is responsible for a majority of breast cancer-related deaths, making it a significant clinical concern1. For cancer to metastasize, cancerous tumor cells must first invade the extracellular matrix and then enter the vasculature by squeezing through small gaps in the vascular endothelium. To establish a metastatic tumor, these cells travel through the body and exit the vasculature by squeezing through these gapsin the endothelium to create satellite tumors1. These gaps in the endothelium are relatively small, ranging from 1.2 to 2 microns in diameter2. Although the cytoplasm of cells may fit through gaps of this size, the nucleus serves as a physical barrier because it has a diameter of about 10–20 microns and a stiffness more than twice that of the cytoplasm3. Nuclear morphology is well-established as an effective diagnostic tool in grading many cancers4. Changes in nuclear morphology and nuclear compliance, such as nuclear softening, is associated with tumor aggressiveness and metastasis5–7, and is recognized as a ‘hallmark of cancer’1,8. This nuclear softening that is associated with cancer progression allows for easier movement of cancer cells through tissues, and through the endothelial slits in the vasculature9. Nuclear and cellular stiffness are also regulated by the stiffness of the tumor microenvironment (TME), caused by increased extracellular matrix (ECM) secreted by the tumor10. Nuclear softness promotes invasion and metastasis, as stiffening of these invasive soft cell populations has been shown to prevent invasion in breast cancer cells11. Nuclear stiffness is governed by a complex set of nucleostructural proteins that serve as signaling molecules and scaffolds. For example, emerin, an inner nuclear membrane protein that binds to lamins, is also responsible for regulating nuclear structure12–14. Interestingly, emerin is reported to be mutated in cancers, specifically in its nucleoskeletal binding domain13. We previously showed that triple-negative breast cancer (TNBC) cell lines have significantly less emerin expression than their non-cancerous controls14. This decreased emerin expression correlated with decreased nuclear size and increased migration and invasion14. Expressing GFP-emerin rescued these deficits, while GFP-emerin mutants that failed to bind nuclear actin and lamins were unable to rescue nuclear size, migration, or invasion14. In mice, we found that expressing wildtype GFP-emerin in MDA-231 cells decreased primary tumor size and lung metastasis compared to MDA-231 cells expressing GFP14. GFPemerin mutants that blocked binding to nuclear a

FAQs

How does emerin deficiency affect MCF7 cells during metastasis?

Emerin deficiency produces smaller, misshapen nuclei and increases nuclear compliance, which supports movement through small endothelial gaps and promotes invasive behavior.

What was tested to confirm the role of emerin in invasiveness?

The authors downregulated emerin in noninvasive MCF7 cells to assess nuclear morphology and migration, and they observed increased impeded cell migration alongside smaller dysmorphic nuclei.

How do patient samples support the clinical relevance of emerin loss?

In 192 breast cancer patient samples, emerin expression inversely correlated with cancer invasiveness, indicating that emerin reduction aligns with progression toward more invasive disease.

Sep 21, 2026

Upload by Asher