Mitotic Stress and Chromosomal Instability in Cancer: The Case for TPX2

Abstract

Cell cycle deregulation is a common motif in human cancer, and multiple therapeutic strategies are aimed to prevent tumor cell proliferation. Whereas most current therapies are designed to arrest cell cycle progression either in G1/S or in mitosis, new proposals include targeting the intrinsic chromosomal instability (CIN, an increased rate of gain or losses of chromosomes during cell division) or aneuploidy (a genomic composition that differs from diploid) that many tumor cells display. Why tumors cells are chromosomally unstable or aneuploid and what are the consequences of these alterations are not completely clear at present. Several mitotic regulators are overexpressed as a consequence of oncogenic alterations, and they are likely to alter the proper regulation of chromosome segregation in cancer cells. In this review, we propose the relevance of TPX2, a mitotic regulator involved in the formation of the mitotic spindle, in oncogene-induced mitotic stress. This protein, as well as its partner Aurora-A, is frequently overexpressed in human cancer, and its deregulation may participate not only in chromosome numeric aberrations but also in other forms of genomic instability in cancer cells.

Endometriosis, Leiomyoma and Adenomyosis: the Risk of Gynecologic Malignancy

“…Genomic instability is a known characteristic of cancer (Pérez de Castro and Malumbres, 2012). Moreover, it is well known that most neoplasms are monoclonal in origin (Teixeira and Heim, 2011).…”

TPX2 expression is associated with poor survival in gastric cancer

“…As a critical regulator of mitosis, TPX2 cooperates with Aurora-A kinase and Eg5 kinesin to control microtubule assembly and spindle stability. TPX2 is required for the formation of normal bipolar spindles and chromosome segregation [9, 10]. …”

Profiling DNA damage response following mitotic perturbations

“…6 for original images of WBs), we propose that our results might reflect what we operationally define here as ‘biological penetrance'. Specifically, recent literature suggests that in addition to their established roles in mitosis, PLK1, TPX2 and CDCA5 (the cluster 3 members and stronger inducers of DDR in the above experiments) may have additional functions in interphase that can directly or indirectly impinge on genome integrity3940414243. We therefore speculate that the mitotic chromosomes are in fact rather resilient and do not break readily when mitotic progression is halted.…”