Tumor Progression to Malignancy: A Discussion of the Unifying Role of the Cytoskeleton

Abstract

Cancers may increase not only quantitatively in size and spread but also qualitatively in grade of malignancy, degree of differentiation, metastatic potential, and genetic variability. Evidence suggests that in many tumors structural aspects of progression to malignancy result from defective control of cytoskeletal components, particularly microtubules. Defective microtubules in the mitotic spindle play a role in asymmetric mitotic divisions that result in hyperploidy and gene amplification or monosomy and possible expression of recessive oncogenes. These defects may give rise to a cascade of reproductive errors whose genetic variability, under selection pressure, provides a mechanism for the evolution of more anaplastic, metastatic, and drug-resistant cell lines. Malignant progression reaffirms the need for early treatment and for focusing therapy of advanced cases on the most metastatic and genetically variable cells.