PRC1: Linking Cytokinesis, Chromosomal Instability, and Cancer Evolution

Cytokinesis defects drive carcinogenesis by creating CIN. CIN causes genetic heterogeneity within tumors and contributes to clonal cancer evolution. PRC1, a master regulator of normal cytokinesis, is deregulated in various types of cancers and this correlates with drug resistance and worse patient outcome. PRC1 emerges as a novel drug target. Targeting PRC1 may attenuate CIN in genomically unstable cancers, or drive genetically stable cancers into apoptosis via generation of genomic chaos. Cytokinesis is the final event of the cell cycle dividing one cell into two daughter cells. The protein regulator of cytokinesis (PRC)1 is essential for cytokinesis and normal cell cleavage. Deregulation of PRC1 causes cytokinesis defects that promote chromosomal instability (CIN) and thus tumor heterogeneity and cancer evolution. Consistently, abnormal PRC1 expression correlates with poor patient outcome in various malignancies, which may be caused by PRC1-mediated CIN and aneuploidy. Here, we review the physiological functions of PRC1 in cell cycle regulation and its contribution to tumorigenesis and intratumoral heterogeneity. We discuss targeting PRC1 within the complementary approaches of either normalizing CIN in aneuploid cancers or creating chromosomal chaos in genomically stable cancers to induce apoptosis. Cytokinesis is the final event of the cell cycle dividing one cell into two daughter cells. The protein regulator of cytokinesis (PRC)1 is essential for cytokinesis and normal cell cleavage. Deregulation of PRC1 causes cytokinesis defects that promote chromosomal instability (CIN) and thus tumor heterogeneity and cancer evolution. Consistently, abnormal PRC1 expression correlates with poor patient outcome in various malignancies, which may be caused by PRC1-mediated CIN and aneuploidy. Here, we review the physiological functions of PRC1 in cell cycle regulation and its contribution to tumorigenesis and intratumoral heterogeneity. We discuss targeting PRC1 within the complementary approaches of either normalizing CIN in aneuploid cancers or creating chromosomal chaos in genomically stable cancers to induce apoptosis. describes the presence of an abnormal number of chromosomes in a cell resulting in anisokaryosis (unequal shapes of the cell nuclei), which is frequently observed in cancer cells. originate from the centrosome and do not have a connection to a kinetochore, but anchor the spindle poles to the plasma membrane. is a genomic state in which chromosomes are unstable, meaning that parts of the chromosomes or even the whole chromosomes are duplicated (gain) or deleted (loss). Upon mitosis, unequal distribution of genetic information to daughter cells can result in in aneuploidy. The majority of human solid cancers is characterized by CIN. interdigitate at the spindle midzone and push the spindle poles apart via motor proteins. protein complexes assembled on both sides the centromeric region of a chromosome. Kinetochores are required for the interaction of spindle microtubules with chromosomes and proper chromosome segregation. bundles of microtubules that end at kinetochores. the only structure linking the two halves of the mitotic spindle. The midzone is initially formed between separating chromosomes by bundling of interpolar microtubules, and then compacted into an electron-dense structure called the midbody. The midzone serves as a platform or ‘landing pad’ for other critical spindle midzone proteins, such as centralspindlin and chromosomal passenger proteins involved in cytokinesis.