PMID- 30206213
OWN - NLM
STAT- MEDLINE
DCOM- 20191113
LR  - 20221007
IS  - 2041-4889 (Electronic)
VI  - 9
IP  - 9
DP  - 2018 Sep 11
TI  - Identification of protein kinase inhibitors to reprogram breast cancer cells.
PG  - 915
LID - 10.1038/s41419-018-1002-2 [doi]
LID - 915
AB  - Direct reversion of cancers into normal-like tissues is an ideal strategy for 
      cancer treatment. Recent reports have showed that defined transcription factors 
      can induce reprogramming of cancer cells into pluripotent stem cells, supporting 
      this notion. Here, we have developed a reprogramming method that uses a 
      conceptually unique strategy for breast cancer cell treatment. We have screened a 
      kinase inhibitor library and found that Rho-associated protein kinase (ROCK) and 
      mammalian target of rapamycin (mTOR) kinase inhibitors can substitute for all 
      transcription factors to be sufficient to reprogram breast cancer cells into 
      progenitor cells. Furthermore, ROCK-mTOR inhibitors could reprogram breast cancer 
      cells to another terminal lineage-adipogenic cells. Genome-wide transcriptional 
      analysis shows that the induced fat-like cells have a profile different from 
      breast cancer cells and similar to that of normal adipocytes. In vitro and in 
      vivo tumorigenesis assays have shown that induced fat-like cells lose 
      proliferation and tumorigenicity. Moreover, reprogramming treatment with 
      ROCK-mTOR inhibitors prevents breast cancer local recurrence in mice. Currently, 
      ROCK-mTOR inhibitors are already used as antitumor drugs in patients, thus, this 
      reprogramming strategy has significant potential to move rapidly toward clinical 
      trials for breast cancer treatment.
FAU - Yuan, Jie
AU  - Yuan J
AD  - Cancer Biology Division, Department of Radiation Oncology, Washington University 
      School of Medicine, Saint Louis, MO, 63108, USA.
AD  - Medical Center of Stomatology, The First Affiliated Hospital of Jinan University, 
      510630, Guangzhou, China.
AD  - School of Stomatology, Jinan University, 510630, Guangzhou, China.
FAU - Zhang, Fan
AU  - Zhang F
AD  - Cancer Biology Division, Department of Radiation Oncology, Washington University 
      School of Medicine, Saint Louis, MO, 63108, USA.
FAU - You, Meng
AU  - You M
AD  - Cancer Biology Division, Department of Radiation Oncology, Washington University 
      School of Medicine, Saint Louis, MO, 63108, USA.
FAU - Yang, Qin
AU  - Yang Q
AD  - Cancer Biology Division, Department of Radiation Oncology, Washington University 
      School of Medicine, Saint Louis, MO, 63108, USA. qyang@wustl.edu.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Retracted Publication
DEP - 20180911
PL  - England
TA  - Cell Death Dis
JT  - Cell death & disease
JID - 101524092
RN  - 0 (Amides)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Pyridines)
RN  - 138381-45-0 (Y 27632)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (rho-Associated Kinases)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
RIN - Cell Death Dis. 2022 Oct 7;13(10):853. PMID: 36207317
MH  - Adipocytes/cytology
MH  - Amides/pharmacology
MH  - Animals
MH  - Antineoplastic Agents/pharmacology
MH  - Breast Neoplasms/*drug therapy/pathology
MH  - Cell Line, Tumor
MH  - Cell Proliferation/drug effects
MH  - Cellular Reprogramming/*drug effects
MH  - Cellular Reprogramming Techniques/*methods
MH  - Female
MH  - Humans
MH  - Mice
MH  - Mice, Inbred NOD
MH  - Mice, SCID
MH  - Pluripotent Stem Cells/*cytology
MH  - Pyridines/pharmacology
MH  - Sirolimus/pharmacology
MH  - TOR Serine-Threonine Kinases/*antagonists & inhibitors
MH  - Xenograft Model Antitumor Assays
MH  - rho-Associated Kinases/*antagonists & inhibitors
PMC - PMC6133942
EDAT- 2018/09/13 06:00
MHDA- 2019/11/14 06:00
PMCR- 2018/09/11
CRDT- 2018/09/13 06:00
PHST- 2018/04/10 00:00 [received]
PHST- 2018/05/11 00:00 [accepted]
PHST- 2018/05/09 00:00 [revised]
PHST- 2018/09/13 06:00 [entrez]
PHST- 2018/09/13 06:00 [pubmed]
PHST- 2019/11/14 06:00 [medline]
PHST- 2018/09/11 00:00 [pmc-release]
AID - 10.1038/s41419-018-1002-2 [pii]
AID - 1002 [pii]
AID - 10.1038/s41419-018-1002-2 [doi]
PST - epublish
SO  - Cell Death Dis. 2018 Sep 11;9(9):915. doi: 10.1038/s41419-018-1002-2.