A USE1ful Biomarker and Molecular Target in Lung Cancer?
Menée à l'aide de lignées cellulaires, de xénogreffes sur des modèles murins et d'échantillons de tissus sains ou tumoraux prélevés sur 106 patients atteints d'un cancer du poumon, cette étude analyse le rôle dans la tumorigenèse de l'enzyme UBA6, une enzyme d'activation de l'ubiquitine identifiée récemment et spécifique de l'enzyme conjugante E2
Despite recent advances in detection and management, lung cancer remains the most frequent cause of cancer-related mortality. According to a World Health Organization report, lung cancer accounted for 1.59 million deaths worldwide in the year 2012 alone (http://www.who.int/mediacentre/factsheets/fs297/en/). While current targeted therapies (such as inhibitors for EGFR and ALK) help some patients, more widely applicable biomarkers/molecular targets are urgently needed. In this issue of the Journal, Kim et al. report that USE1, a Uba6-specific ubiquitin conjugating E2 enzyme, is frequently overexpressed (92.45%) in lung cancers compared with normal lung tissues (1). While sample size was relatively limited (106 paired cancer and adjacent nontumor lung tissues), the strikingly high frequency of USE1 overexpression in tumors suggests that USE1 may serve as a useful lung cancer biomarker and perhaps a novel molecular target. The ubiquitin-conjugating enzyme USE1/UBE2Z is in the middle of an E1-E2-E3 ubiquitin transfer cascade and plays a major role in protein homeostasis (proteostasis). It functions downstream of and specifically with the ubiquitin-activating enzyme (E1) UBA6 to attach ubiquitin or FAT10 via ubiquitin-ligase E3 (eg, UBR1-3) to proteins to mark them for degradation by the proteasome (2,3). Embryonic ablation of the UBA6-USE1 system in mice is lethal, and its brain-specific knockout results in abnormal neuron patterning, with the afflicted mice displaying impaired social behavior (4). In this report, Kim et al. explored the clinical significance of USE1 in lung cancers. Comparing paired cancer and adjacent nontumor lung tissues, Kim et al. found that USE1 protein levels were statistically significantly elevated …