Abstract 5805: Myosin 1e colocalization with β1-intergin and association with tumor progression in colorectal cancer

Abstract

Abstract For colorectal cancer (CRC), the risk of relapse among stage II and stage III a/b patients is 20-30% and the benefit of treating these patients with chemotherapy is uncertain. As a result, many patients are undertreated, putting them at increased risk for disease relapse, or overtreated, exposing them to unnecessary and harmful chemotherapy with little potential benefit. Therefore, defining prognostic biomarkers to more accurately determine each person’s risk of relapse and need for chemotherapy is a priority in CRC research. Promising targets for biomarker discovery are actin-binding proteins. As a broad class, these proteins regulate the actin cytoskeleton and serve as direct, proximal regulators of invasive and metastatic phenotypes. Further, the prognostic utility of several of these proteins has recently been reported in the literature. Myosin 1e (Myo1e) a long-tailed, class I myosin, is one such protein with proposed clinical utility as a prognostic biomarker. In kidney podocyte cells, Myo1e regulates endocytosis, adhesion, migration, and invadosome dynamics. Despite its expression in numerous cancers, the functional role of Myo1e specifically in cancer cells and its association with tumor progression remains elusive. To define a role in cancer cells, the localization of Myo1e was examined in vitro by immunofluorescence in T84 human CRC cells. Myo1e co-localized with actin, cortactin and β1 integrin at membrane ruffles, which regulate integrin endocytosis and trafficking. Interestingly, both Myo1e and β1 integrin also co-localized with caveolin-1, a regulator of integrin endocytosis, suggesting Myo1e expression may regulate caveolae-dependent integrin endocytosis and trafficking. To evaluate potential prognostic utility, Myo1e expression in colorectal tumors and matched normal adjacent tissue (NAT) was examined by immunohistochemistry in a tissue microarray constructed from duplicate tissue cores from 119 CRC patients. The patient cohort was well balanced across TNM stage: stage 0 (10.1%), stage 1 (20.2%), stage 2 (26.9%), stage 3 (31.1%), and stage 4 (12.6%), and the majority (68.9%) of CRC tissues examined were of moderate tumor grade. The ratio of Myo1e expression in tumors compared to NAT was significantly correlated with clinicopathologic indicators of disease progression, including clinical stage, depth of invasion at the primary tumor (T-score), and lymph node metastasis. Together, these data suggest Myo1e expression correlates with tumor progression and may regulate invasive phenotypes through integrin trafficking pathways. Examining the prognostic utility and biologic function of Myo1e may a define a novel biomarker with translational utility for improved clinical management of colorectal cancer patients. Citation Format: Jeffrey Pfannenstein, Filippo Bori, Alessandro Bombonati, David Zuzga. Myosin 1e colocalization with β1-intergin and association with tumor progression in colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5805. doi:10.1158/1538-7445.AM2017-5805