PURPOSE: To determine the role of the mammalian target of rapamycin (mTOR) signaling in sustaining cancer stem-like cells and its clinical values in colorectal cancer (CRC). METHODS: mTOR expression in CRC patients was analyzed by immunohistochemistry and survival analysis was used to confirm the clinical value of mTOR. Colorectal cell lines were treated by mTOR inhibitors rapamycin and PP242, and sphere formation assay and aldehyde dehydrogenase (ALDH) assay were utilized to determine the impact of mTOR inhibition in CRC stem-like cells, combined or not combined with chemotherapeutic drug (fluorouracil and oxaliplatin). RESULTS: mTOR expression was associated with outcomes of CRC patients and predicted poor prognosis in stage II CRC patients. mTOR signaling was activated in stem-like colorectal cancer cells, and mTOR inhibitors (rapamycin and PP242) decreased the capacity of sphere formation as well as ALDH activity. Furthermore, mTOR inhibitors also were demonstrated to suppress the stimulation of stem-like cells by chemotherapy. CONCLUSIONS: mTOR shared predictive significance in stage II CRC patients' outcomes and played a vital role in the maintenance of colorectal cancer stem-like cells. mTOR inhibitors might hold the potential to become a therapeutic target against CRC stem cells.
PURPOSE: To determine the role of the mammalian target of rapamycin (mTOR) signaling in sustaining cancer stem-like cells and its clinical values in colorectal cancer (CRC). METHODS:mTOR expression in CRC patients was analyzed by immunohistochemistry and survival analysis was used to confirm the clinical value of mTOR. Colorectal cell lines were treated by mTOR inhibitors rapamycin and PP242, and sphere formation assay and aldehyde dehydrogenase (ALDH) assay were utilized to determine the impact of mTOR inhibition in CRC stem-like cells, combined or not combined with chemotherapeutic drug (fluorouracil and oxaliplatin). RESULTS:mTOR expression was associated with outcomes of CRC patients and predicted poor prognosis in stage II CRC patients. mTOR signaling was activated in stem-like colorectal cancer cells, and mTOR inhibitors (rapamycin and PP242) decreased the capacity of sphere formation as well as ALDH activity. Furthermore, mTOR inhibitors also were demonstrated to suppress the stimulation of stem-like cells by chemotherapy. CONCLUSIONS:mTOR shared predictive significance in stage II CRC patients' outcomes and played a vital role in the maintenance of colorectal cancer stem-like cells. mTOR inhibitors might hold the potential to become a therapeutic target against CRC stem cells.
Authors: Silvana Papagerakis; Giuseppe Pannone; Li Zheng; Imad About; Nawar Taqi; Nghia P T Nguyen; Margarite Matossian; Blake McAlpin; Angela Santoro; Jonathan McHugh; Mark E Prince; Petros Papagerakis Journal: Exp Cell Res Date: 2014-05-05 Impact factor: 3.905
Authors: Nathaniel Melling; Ronald Simon; Jakob R Izbicki; Luigi M Terracciano; Carsten Bokemeyer; Guido Sauter; Andreas H Marx Journal: Int J Clin Exp Pathol Date: 2015-06-01
Authors: Anna Kornakiewicz; Wojciech Solarek; Zofia F Bielecka; Fei Lian; Cezary Szczylik; Anna M Czarnecka Journal: Curr Signal Transduct Ther Date: 2014-12
Authors: Claudia Maletzki; Maja Huehns; Patrick Knapp; Nancy Waukosin; Ernst Klar; Friedrich Prall; Michael Linnebacher Journal: PLoS One Date: 2015-11-30 Impact factor: 3.240