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Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Sep 15, 2022; 14(9): 1637-1653
Published online Sep 15, 2022. doi: 10.4251/wjgo.v14.i9.1637
Emerging role of caldesmon in cancer: A potential biomarker for colorectal cancer and other cancers
Alya R Alnuaimi, Vidhya A Nair, Lara J Bou Malhab, Eman Abu-Gharbieh, Anu Vinod Ranade, Gianfranco Pintus, Mohamad Hamad, Hauke Busch, Jutta Kirfel, Rifat Hamoudi, Wael M Abdel-Rahman
Alya R Alnuaimi, Vidhya A Nair, Lara J Bou Malhab, Eman Abu-Gharbieh, Anu Vinod Ranade, Gianfranco Pintus, Mohamad Hamad, Rifat Hamoudi, Wael M Abdel-Rahman, Sharjah Institute for Medical Research, University of Sharjah, Sharjah 27272, United Arab Emirates
Alya R Alnuaimi, College of Medicine, University of Sharjah, Sharjah 27272, United Arab Emirates
Eman Abu-Gharbieh, Rifat Hamoudi, Department of Clinical Sciences, University of Sharjah, Sharjah 27272, United Arab Emirates
Anu Vinod Ranade, Department of Basic Medical Sciences, University of Sharjah, Sharjah 27272, United Arab Emirates
Gianfranco Pintus, Mohamad Hamad, Wael M Abdel-Rahman, Department of Medical Laboratory Sciences, University of Sharjah, Sharjah 27272, United Arab Emirates
Gianfranco Pintus, Department of Biomedical Sciences, University of Sassari, Sassari 07100, Italy
Hauke Busch, University Cancer Center Schleswig-Holstein and Luebeck Institute for Experimental Dermatology, University of Luebeck, Luebeck 23560, Germany
Jutta Kirfel, Institute of Pathology, University Hospital Schleswig-Holstein, Luebeck 23560, Germany
Rifat Hamoudi, Division of Surgery and Interventional Science, University College London, London WC1E 6BT, United Kingdom
Author contributions: Alnuaimi AR performed the literature search; Abdel-Rahman WM proposed and designed the review, obtained funds, performed the literature search; Nair VA, Malhab LJB, Hamad M, Hamoudi R, Abu-Gharbieh E, Ranade A, Pintus G, Kirfel J, and Busch H edited the manuscript; Alnuaimi AR and Abdel-Rahman WM collected the data, and wrote parts of the manuscript; Alnuaimi AR, Abdel-Rahman WM, Nair VA, Malhab LJB, Hamad M, Hamoudi R, Abu-Gharbieh E, Ranade AV, Pintus G, Kirfel J, and Busch H contributed to the data analysis; and all authors revised/endorsed the final draft.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Wael M Abdel-Rahman, MD, PhD, Professor, Department of Medical Laboratory Sciences, University of Sharjah, University City, Sharjah 27272, United Arab Emirates. whassan@sharjah.ac.ae
Received: March 16, 2022
Peer-review started: March 16, 2022
First decision: April 17, 2022
Revised: May 5, 2022
Accepted: July 26, 2022
Article in press: July 26, 2022
Published online: September 15, 2022
Processing time: 177 Days and 12.4 Hours
Abstract

Colorectal cancer (CRC) is a devastating disease, mainly because of metastasis. As a result, there is a need to better understand the molecular basis of invasion and metastasis and to identify new biomarkers and therapeutic targets to aid in managing these tumors. The actin cytoskeleton and actin-binding proteins are known to play an important role in the process of cancer metastasis because they control and execute essential steps in cell motility and contractility as well as cell division. Caldesmon (CaD) is an actin-binding protein encoded by the CALD1 gene as multiple transcripts that mainly encode two protein isoforms: High-molecular-weight CaD, expressed in smooth muscle, and low-molecular weight CaD (l-CaD), expressed in nonsmooth muscle cells. According to our comprehensive review of the literature, CaD, particularly l-CaD, plays a key role in the development, metastasis, and resistance to chemoradiotherapy in colorectal, breast, and urinary bladder cancers and gliomas, among other malignancies. CaD is involved in many aspects of the carcinogenic hallmarks, including epithelial mesenchymal transition via transforming growth factor-beta signaling, angiogenesis, resistance to hormonal therapy, and immune evasion. Recent data show that CaD is expressed in tumor cells as well as in stromal cells, such as cancer-associated fibroblasts, where it modulates the tumor microenvironment to favor the tumor. Interestingly, CaD undergoes selective tumor-specific splicing, and the resulting isoforms are generally not expressed in normal tissues, making these transcripts ideal targets for drug design. In this review, we will analyze these features of CaD with a focus on CRC and show how the currently available data qualify CaD as a potential candidate for targeted therapy in addition to its role in the diagnosis and prognosis of cancer.

Keywords: Bladder cancer; CALD1; Caldesmon; Chemoresistance; Colorectal cancer; Gastric cancer; Glioma; Epithelial to mesenchymal transition; Invasion; Metastasis

Core Tip: The actin-binding protein caldesmon (CaD) plays an important role in cancer development, metastasis, and resistance to chemotherapy. CaD has emerged as a significant player in carcinogenesis, as it features many cancer hallmarks, including epithelial mesenchymal transition, angiogenesis, and immune evasion. Interestingly, CaD undergoes selective tumor-specific splicing, and the resulting isoforms are generally not expressed in normal tissues. These data qualify CaD as an attractive candidate for targeted therapy in addition to its role in the diagnosis and prognosis of cancer.