title: Significance of mTOR signaling and its inhibitor against cancer stem-like cells in colorectal cancer.
abstract: OBJECTIVE
  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.affiliation: Department of Colorectal Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Zerong
authors.initials: Z
authors.lastname: Cai
authors.forename: Jia
authors.initials: J
authors.lastname: Ke
authors.forename: Xiaosheng
authors.initials: X
authors.lastname: He
authors.forename: Ruixue
authors.initials: R
authors.lastname: Yuan
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Chen
authors.forename: Xianrui
authors.initials: X
authors.lastname: Wu
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.forename: Jianping
authors.initials: J
authors.lastname: Wang
authors.forename: Ping
authors.initials: P
authors.lastname: Lan
authors.forename: Xiaojian
authors.initials: X
authors.lastname: Wu
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D002288:Adenocarcinoma, Mucinous / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D011379:Prognosis; D020123:Sirolimus / Q000008:administration & dosage; D015996:Survival Rate; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D005472:Fluorouracil; D020123:Sirolimus