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Regulation of Cell Adhesion and Migration via Microtubule Cytoskeleton Organization, Cell Polarity, and
Narendra Thapa1, Tianmu Wen1, Vincent L Cryns1,2
1The Carbone Cancer Center, School of Medicine and Public Health, University of Wisconsin-Madison, 1111 Highland Avenue, Madison, WI 53705, USA.
Abstract:
The capacity for cancer cells to metastasize to distant organs depends on their ability to execute the carefully choreographed processes of cell adhesion and migration. As most human cancers are of epithelial origin (carcinoma), the transcriptional downregulation of adherent/tight junction proteins (e.g., E-cadherin, Claudin and Occludin) with the concomitant gain of adhesive and migratory phenotypes has been extensively studied. Most research and reviews on cell adhesion and migration focus on the actin cytoskeleton and its reorganization. However, metastasizing cancer cells undergo the extensive reorganization of their cytoskeletal system, specifically in originating/nucleation sites of microtubules and their orientation (e.g., from non-centrosomal to centrosomal microtubule organizing centers). The precise mechanisms by which the spatial and temporal reorganization of microtubules are linked functionally with the acquisition of an adhesive and migratory phenotype as epithelial cells reversibly transition into mesenchymal cells during metastasis remains poorly understood. In this Special Issue of "Molecular Mechanisms Underlying Cell Adhesion and Migration", we highlight cell adhesion and migration from the perspectives of microtubule cytoskeletal reorganization, cell polarity and phosphoinositide signaling.
Insights
Cancer cell metastasis relies on cell adhesion and migration. This study explores how microtubule reorganization, not just actin, drives these essential processes during epithelial-to-mesenchymal transition.
Area of Science:
- Cell Biology
- Cancer Research
- Molecular Biology
Background:
- Metastasis, a hallmark of cancer, involves cell adhesion and migration.
- Epithelial cancers often downregulate junction proteins, promoting migration.
- Current research primarily focuses on the actin cytoskeleton's role in cell migration.
Purpose of the Study:
- To investigate the underappreciated role of microtubule reorganization in cancer cell metastasis.
- To elucidate the mechanisms linking microtubule dynamics to epithelial-mesenchymal transition.
- To highlight the interplay between cell adhesion, migration, microtubule cytoskeleton, cell polarity, and phosphoinositide signaling.
Main Methods:
- Focus on microtubule cytoskeletal reorganization.
- Analysis of cell polarity.
- Investigation of phosphoinositide signaling pathways.
Main Results:
- Metastatic cancer cells extensively reorganize their microtubule cytoskeleton.
- Microtubule organizing centers shift during epithelial-mesenchymal transition.
- The functional link between microtubule reorganization and migratory phenotype acquisition is explored.
Conclusions:
- Microtubule dynamics are crucial for cancer cell metastasis.
- Understanding microtubule reorganization offers new therapeutic targets.
- This work emphasizes a multi-faceted approach to cell adhesion and migration research.
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