Abstract
Tumorigenesis is a long-term and multistage process that often leads to the formation of metastases. During this pathological course, two major events appear to be crucial: primary tumour growth and metastatic expansion. In this context, despite research and clinical advances during the past decades, bone cancers remain a leading cause of death worldwide among paediatric cancer patients. Osteosarcomas are the most common malignant bone tumours in children and adolescents. Notwithstanding advances in therapeutic treatments, many patients succumb to these diseases. In particular, less than 30% of patients who demonstrate metastases at diagnosis or are poor responders to chemotherapy survive 5 years after initial diagnosis. LIM kinases (LIMKs), comprising LIMK1 and LIMK2, are common downstream effectors of several signalization pathways, and function as a signalling node that controls cytoskeleton dynamics through the phosphorylation of the cofilin family proteins. In recent decades, several reports have indicated that the functions of LIMKs are mainly implicated in the regulation of actin microfilament and the control of microtubule dynamics. Previous studies have thus identified LIMKs as cancer-promoting regulators in multiple organ cancers, such as breast cancer or prostate cancer. This review updates the current understanding of LIMK involvement in osteosarcoma progression.
Highlights
Whereas the 5-year survival rate is greater than 78% in the absence of metastases at diagnosis or for good responders, this survival rate drops to 25% for metastatic or recurrent
Three splice variants were identified: LIMK2a and LIMK2b, which code for a smaller protein, and LIM kinase 2 (LIMK2)-1, which generates a protein corresponding to the N-terminal variant 1 and C-terminal variant 2ab
The cumulative evidence demonstrates the relevance of targeting LIM kinases (LIMKs) in OS
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Despite advances in the therapeutic treatment of osteosarcoma (OS), the leading malignant bone tumour in children and adolescents, many patients die from this disease. These survival rates, which have shown little or no improvement in recent decades, underscore the urgent need to develop new therapeutic strategies. In this context, LIM kinases (LIMKs), which play a major role in controlling actin microfilament dynamics and microtubule (MT) dynamics, have been described as regulators of the development of multiple cancers
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