Mechanosensor MYL9 regulates cancer cell malignancy in gastrointestinal tumors

Although the stiffness of tissues likely is involved in the malignant behavior of tumors, it remains to be clarified which molecules control the nature, how it is involved in the invasiveness of tumors, or whether any marker is available for the prediction of cancer patient prognosis. In the present study, we studied the role of Myl9, a non-muscle-type, myosin light chain by the experiment in vitro, and assessed the usefulness in the stratification of patients in vivo as the precision medicine. Given that Myl9 is involved in the contraction of cell skeleton, cell hardness, and alterations of cell morphology in various tissues, we first examined whether the expression of the Myl9 is associated with the clinical status of tumors by immunohistochemistry. The results of 45 cases with colon cancer and pancreatic cancer indicated that the increased expression of Myl9 is associated significantly with a reduced provability of overall survival and disease-free survival of those cancers. Moreover, we noted the differential expression of Myl9 in epithelial cancer cells and mesenchymal fibroblasts, i.e., the accumulation of Myl9 staining in cell nuclei of fibroblasts. The experiment of 3-dimensional culture with cancer cells and fibroblasts confirmed the results. Furthermore, we investigated whether Myl9 overexpression is involved in the biologic behavior of gastrointestinal cancer cells. The results showed that the rentiviral-mediated overexpression of Myl9 resulted in an increase of cell proliferation and invasion as well as tumorigenicity in mice. The present study indicates that Myl9 protein can play a fundamental role in the malignant behaviors of gastrointestinal cancer cells. Citation Format: Masamitsu Konno, Kiminori Yanagisawa, Katsunori Matsushita, Ayumu Asai, Jun Koseki, Michiya Matsusaki, Shinji Deguchi, Yuichiro Doki, Masaki Mori, Hideshi Ishii. Mechanosensor MYL9 regulates cancer cell malignancy in gastrointestinal tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5164.