Department of Biochemistry and Tissue Biology, University of Campinas, UNICAMP, Campinas, SP, Brazil.
Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center Rotterdam, PO Box 2040, 3000 CA, Rotterdam, The Netherlands.
Mol Cell Biochem. 2020 Mar;466(1-2):83-89. doi: 10.1007/s11010-020-03690-1. Epub 2020 Feb 4.
In the last decade, several reports highlight the importance of the low molecular weight protein tyrosine phosphatase (LMWPTP) in cancer aggressiveness and resistance. Specifically, in chronic myeloid leukemia, we have reported that high expression of the LMWPTP maintains Src and Bcr-Abl kinases in an activated status and the glucose metabolism is directed to lactate production and, in turn, favor the pentoses pathway (one of the key process for antioxidant and protective responses). In this present study, we investigated the possible correlation between the LMWPTP and autophagy. In resistant chronic myeloid leukemia cells, the antioxidant response is supported by the glycolytic metabolism and antioxidant enzymes such as SOD and catalase, both favored by the LMWPTP. Therefore, when the cells were challenged by hydrogen peroxide treatment, the LMWPTP level goes down as well as SOD, and in turn, autophagy process was stimulated. The findings presented here reveal a novel aspect by which LMWPTP cooperates for the resistance of CML towards stressor stimuli.
在过去的十年中,有几项报告强调了低分子量蛋白酪氨酸磷酸酶(LMWPTP)在癌症侵袭性和耐药性中的重要性。具体来说,在慢性髓系白血病中,我们已经报道过高表达的 LMWPTP 使Src 和 Bcr-Abl 激酶保持激活状态,并且葡萄糖代谢被导向乳酸生成,进而有利于戊糖途径(抗氧化和保护反应的关键过程之一)。在本研究中,我们研究了 LMWPTP 和自噬之间可能存在的相关性。在耐药性慢性髓系白血病细胞中,抗氧化反应由糖酵解代谢和抗氧化酶(如 SOD 和过氧化氢酶)支持,而这些酶都受到 LMWPTP 的促进。因此,当细胞受到过氧化氢处理的挑战时,LMWPTP 水平以及 SOD 都会下降,自噬过程会被刺激。本研究揭示了 LMWPTP 通过合作来帮助 CML 抵抗应激刺激的一个新方面。