Targeting Aurora Kinase A Inhibits Hypoxia-Mediated Neuroblastoma Tumor Progression

CEP41‐mediated ciliary tubulin glutamylation drives angiogenesis through AURKA‐dependent deciliation

“…Thus, we first asked whether hypoxia affects deciliation and tubulin glutamylation in EC cilia, both of which are controlled by CEP41-AURKA molecular axis in the process of angiogenesis. As expected, hypoxic HUVECs show increased mRNA levels of VEGFA and VEGFR2, which are transcriptional targets of both HIF1a [41,42] and AURKA [38,39]. We found HUVECs exposed to 3 and 4 h of hypoxia show significant increases in ciliary resorption (Fig EV4A-D) and tubulin glutamylation ( Fig EV4E).…”

The Different Routes to Metastasis via Hypoxia-Regulated Programs

“…Third, the majority of published studies have used invasion through Matrigel, an arti cial matrix composed of laminin, nidogen, and collagen, which has been measured to dramatically alter tumor cell migration mode (collective vs. single cell), velocity, and distance of migration depending upon its mechanical properties [20]. Even in a study that avoided Matrigel – which contains several extracellular matrix (ECM) molecules including laminin as a major component – and instead utilized only collagen I [21], the situation was not improved as differences in ECM stiffness can dramatically impact migration and invasion. For example, focal adhesion formation and cell motility were enhanced on cultures utilizing a stiff versus a soft substratum, and this effect of substrate stiffness was dependent upon HIF activity, confounding any ability to determine the role HIF activity plays in motility phenotypes [22].…”

“…has been linked to a more aggressive tumor phenotype, usually measured by in vitro parameters of motility and invasion, but also through measurements of lung colonization and metastasis development [21,119,129–139]. …”

Some leopards can change their spots: potential repositioning of stem cell reprogramming compounds as anti-cancer agents

“…Moreover, reversine was shown to inhibit signaling mediated by focal adhesion kinase , which is a key regulator of cancer cell invasion and migration (Avallone et al 2015). It has been demonstrated that the reversine target, aurora kinase, also regulates focal adhesion kinase activity (Romain et al 2014). Cancer progression is not only dependent upon the cancer cells themselves but also results from a complex communication network involving cancer cells and noncancer cells, such as stromal fibroblasts and tumorassociated macrophages, which is termed the tumor microenvironment (reviewed in (Junttila and de Sauvage 2013)).…”