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Annals of Surgical Oncology

, Volume 21, Issue 1, pp 179–188 | Cite as

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

  • Zerong Cai
  • Jia Ke
  • Xiaosheng He
  • Ruixue Yuan
  • Yufeng Chen
  • Xianrui Wu
  • Lei Wang
  • Jianping Wang
  • Ping Lan
  • Xiaojian Wu
Colorectal Cancer

Abstract

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.

Keywords

Rapamycin Oxaliplatin mTOR Inhibitor mTOR Signaling SW480 Cell Line 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgment

The work was supported by the Natural Science Foundation of Guangdong Province, China (No. 10151008901000112), National Natural Science Foundation of China (No. 91029702) and International S&T Cooperation Program of China (No. 2013DFG32990). No potential conflict of interest with the research, authorship, and/or publication exists in this article.

Supplementary material

10434_2013_3146_MOESM1_ESM.doc (43 kb)
Supplementary material 1 (DOC 43 kb)

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Copyright information

© Society of Surgical Oncology 2013

Authors and Affiliations

  • Zerong Cai
    • 1
  • Jia Ke
    • 1
  • Xiaosheng He
    • 1
  • Ruixue Yuan
    • 2
  • Yufeng Chen
    • 1
  • Xianrui Wu
    • 1
  • Lei Wang
    • 1
    • 2
  • Jianping Wang
    • 1
    • 2
  • Ping Lan
    • 1
    • 2
  • Xiaojian Wu
    • 1
    • 2
  1. 1.Department of Colorectal SurgeryThe Sixth Affiliated Hospital of Sun Yat-sen UniversityGuangzhouPeople’s Republic of China
  2. 2.Gastrointestinal Institute of Sun Yat-sen UniversityGuangzhouPeople’s Republic of China

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