AlNuaimi A, Nair VA, Al-Khayyal N, Suliman A, Bou Malhab LJ, Hamoudi R, Hamad M, Talaat IM, Abdel-Rahman WM. Overexpression of low-molecular-weight caldesmon is associated with aggressive phenotypes and epithelial-mesenchymal transition in breast cancer cells. World J Clin Oncol 2026; 17(5): 116662 [DOI: 10.5306/wjco.v17.i5.116662]
Corresponding Author of This Article
Wael M Abdel-Rahman, MD, PhD, Professor, Department of Medical Laboratory Sciences, College of Health Sciences, University of Sharjah, University City, Sharjah 27272, United Arab Emirates. whassan@sharjah.ac.ae
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Medical Laboratory Technology
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Basic Study
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May 24, 2026 (publication date) through May 23, 2026
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World Journal of Clinical Oncology
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AlNuaimi A, Nair VA, Al-Khayyal N, Suliman A, Bou Malhab LJ, Hamoudi R, Hamad M, Talaat IM, Abdel-Rahman WM. Overexpression of low-molecular-weight caldesmon is associated with aggressive phenotypes and epithelial-mesenchymal transition in breast cancer cells. World J Clin Oncol 2026; 17(5): 116662 [DOI: 10.5306/wjco.v17.i5.116662]
World J Clin Oncol. May 24, 2026; 17(5): 116662 Published online May 24, 2026. doi: 10.5306/wjco.v17.i5.116662
Overexpression of low-molecular-weight caldesmon is associated with aggressive phenotypes and epithelial-mesenchymal transition in breast cancer cells
Alya AlNuaimi, Vidhya A Nair, Noura Al-Khayyal, Ashna Suliman, Lara J Bou Malhab, Rifat Hamoudi, Mohamad Hamad, Iman M Talaat, Wael M Abdel-Rahman
Alya AlNuaimi, Mohamad Hamad, Wael M Abdel-Rahman, Department of Medical Laboratory Sciences, College of Health Sciences, University of Sharjah, Sharjah 27272, United Arab Emirates
Alya AlNuaimi, Vidhya A Nair, Noura Al-Khayyal, Ashna Suliman, Lara J Bou Malhab, Rifat Hamoudi, Mohamad Hamad, Iman M Talaat, Wael M Abdel-Rahman, Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah 27272, United Arab Emirates
Rifat Hamoudi, Iman M Talaat, Department of Clinical Sciences, College of Medicine, University of Sharjah, Sharjah 27272, United Arab Emirates
Co-corresponding authors: Alya AlNuaimi and Wael M Abdel-Rahman.
Author contributions: AlNuaimi A performed the laboratory experiments, conducted data analysis, drafted parts of the manuscript; Nair VA, Al-Khayyal N, and Suliman A assisted with and performed specific experimental procedures; Bou Malhab LJ, Hamoudi R, and Hamad M contributed to supervision and data analysis; Talaat IM supplied patient materials; Abdel-Rahman WM proposed and designed the study, secured funding, conducted the literature review, supervised the work, analyzed data, contributed to manuscript writing; AlNuaimi A and Abdel-Rahman WM contributed equally to this article, they are the co-corresponding authors of this manuscript; and all authors critically reviewed, revised, and approved the final manuscript.
Institutional review board statement: This study was approved by the Medical Ethics Committee of University of Sharjah Research and Ethics Committee, approval No. REC-18-01-27-01.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: The underlying data (anonymized) are available from Alya AlNuaimi upon reasonable request at alya.alnuaimi@sharjah.ac.ae.
Corresponding author: Wael M Abdel-Rahman, MD, PhD, Professor, Department of Medical Laboratory Sciences, College of Health Sciences, University of Sharjah, University City, Sharjah 27272, United Arab Emirates. whassan@sharjah.ac.ae
Received: November 18, 2025 Revised: January 27, 2026 Accepted: March 2, 2026 Published online: May 24, 2026 Processing time: 184 Days and 9.4 Hours
Abstract
BACKGROUND
Caldesmon (CAD) has emerged as a promising biomarker of tumor progression and therapeutic response.
AIM
To investigate the expression and functional role of the low-molecular-weight isoform of CAD (l-CAD, about 65 kDa) in breast cancer.
METHODS
We analyzed the expression of l-CAD in breast cancer cell lines enriched for triple-negative breast cancer (TNBC) and in formalin-fixed, paraffin-embedded breast cancer tissues by western blotting and immunohistochemistry, respectively. This was followed by l-CAD silencing and functional analyses. In silico analyses were performed to validate the findings.
RESULTS
L-CAD expression was highly elevated in TNBC cell lines. Silencing of the CALD1 gene in the CAL-51 cell line resulted in the downregulation of mesenchymal markers, upregulation of epithelial markers, and a reduction in cell motility and invasiveness. Transcript-specific reverse transcription-polymerase chain reaction revealed that the low-molecular-weight transcript variant 2 (WI-38 l-CAD II) of CALD1 was the predominant isoform driving tumorigenesis in TNBC cell lines. Immunohistochemical analysis of breast cancer tissues confirmed significant l-CAD expression in the cytoplasm of cancer cells and stromal cells, with significant associations with lymphovascular invasion and human epidermal growth factor receptor 2, estrogen receptor, and progesterone receptor status. Survival analysis demonstrated that high CALD1 expression in TNBC was associated with poor prognosis and reduced disease-free survival.
CONCLUSION
Taken together, these findings highlight that l-CAD overexpression may drive metastasis in TNBC through epithelial-mesenchymal transition and support its relevance as a prognostic biomarker.
Core Tip: Low-molecular-weight caldesmon (l-CAD) plays a key role in triple-negative breast cancer (TNBC) progression by promoting epithelial-mesenchymal transition and enhancing cell motility and invasiveness. This study identifies CALD1 transcript variant 2 as the key isoform driving tumorigenesis in TNBC. Immunohistochemical analysis confirmed l-CAD expression in the cytoplasm of cancer cells and stromal cells, with significant associations with lymphovascular invasion and receptor status. High CALD1 levels in TNBC are associated with poor prognosis and reduced disease-free survival, highlighting l-CAD as a potential driver of metastasis and a promising prognostic biomarker.
