Published online Sep 15, 2022. doi: 10.4251/wjgo.v14.i9.1637
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
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.
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.