mTOR signal transduction pathways contribute to TN-C FNIII A1 overexpression by mechanical stress in osteosarcoma cells

• Published in: Molecules and cells Vol. 37; no. 2; pp. 118 - 125
• Main Authors: Zheng, Lianhe, Zhang, Dianzhong, Zhang, Yunfei, Wen, Yanhua, Wang, Yucai
• Format: Journal Article
• Language: English
• Published: United States Korea Society for Molecular and Cellular Biology 01.02.2014; 한국분자세포생물학회
• Subjects: Adaptor Proteins, Signal Transducing - metabolism; Cell Cycle Proteins; Cell Line, Tumor; Cell Movement; Gene Expression Regulation, Neoplastic; Humans; Osteosarcoma - metabolism; Osteosarcoma - pathology; Phosphoproteins - metabolism; Ribosomal Protein S6 Kinases, 70-kDa - metabolism; Signal Transduction; Stress, Mechanical; Tenascin - genetics; Tenascin - metabolism; TOR Serine-Threonine Kinases - metabolism; 생물학
• ISSN: 1016-8478; 0219-1032
• DOI: 10.14348/molcells.2014.2247

Osteosarcoma is the most common primary malignant bone tumor with a very poor prognosis. Treating osteosarcoma remains a challenge due to its high transitivity. Tenascin-C, with large molecular weight variants including different combinations of its alternative spliced FNIII repeats, is specifically over expressed in tumor tissues. This study examined the expression of Tenascin-C FNIIIA1 in osteosarcoma tissues, and estimated the effect of mechanical stimulation on A1 expression in MG-63 cells. Through immunohistochemical analysis, we found that the A1 protein was expressed at a higher level in osteosarcoma tissues than in adjacent normal tissues. By cell migration assay, we observed that there was a significant correlation between A1 expression and MG-63 cell migra-tion. The relation is that Tenascin-C FNIIIA1 can promote MG-63 cell migration. According to our further study into the effect of mechanical stimulation on A1 expression in MG-63 cells, the mRNA and protein levels of A1 were significantly up-regulated under mechanical stress with the mTOR molecule proving indispensable. Meanwhile, 4E-BP1 and S6K1 (downstream molecule of mTOR) are necessary for A1 normal expression in MG-63 cells whether or not mechanical stress has been encountered. We found that Tenascin-C FNIIIA1 is over-expressed in osteosar-coma tissues and can promote MG-63 cell migration. Furthermore, mechanical stress can facilitate MG-63 cell migration though facilitating A1 overexpression with the necessary molecules (mTOR, 4E-BP1 and S6K1). In con-clusion, high expression of A1 may promote the meta-stasis of osteosarcoma by facilitating MG-63 cell migration. Tenascin-C FNIIIA1 could be used as an indicator in metastatic osteosarcoma patients.