Significance of mTOR Signaling and Its Inhibitor Against Cancer Stem-Like Cells in Colorectal Cancer

Significance of mTOR Signaling and Its Inhibitor Against Cancer Stem-Like Cells in Colorectal Cancer
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mTOR 信号传导及其抑制剂对结直肠癌中癌症干细胞样细胞的意义

DOI:
10.1245/s10434-013-3146-8
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发表时间:
2014-01-01
影响因子:
3.7
通讯作者:
Wu, Xiaojian
Wu, Xiaojian
中科院分区:
医学2区
文献类型:
--
作者:
Cai, Zerong;Ke, Jia;Wu, Xiaojian

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PurposeTo 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).MethodsmTOR 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).ResultsmTOR 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.ConclusionsmTOR 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.