The Role of Plectin Dysregulation in Cancer: Recent Advances

Plectin is a key cytolinker protein that functions as an integrator of the cytoskeletal networks by crosslinking intermediate filaments with actin filaments and microtubules. Mutations or function deficiencies of plectin lead to tissue disorders, particularly affecting the skin, muscle, and nervous tissues. Interestingly, plectin dysregulation in cancer, characterized by aberrant expression and mislocalization, has been increasingly observed, suggesting distinct roles in tumorigenesis and progression. Here, we focus on recent advances regarding the roles of plectin dysregulation in promoting cell proliferation, suppressing cell apoptosis, sustaining the stemness of cancer stem cells, and driving invasion and metastasis. We also discuss its bidirectional interplay with the tumor microenvironment, including modulating immune and inflammatory responses, promoting angiogenesis, sensing and transmitting mechanical cues from the extracellular matrix, and contributing to matrix remodeling. Finally, we highlight emerging therapeutic strategies that target plectin dysregulation with anticancer activity. By summarizing these advances, we aim to enhance the understanding of plectin dysregulation in cancer and illuminate its potential as a therapeutic target.