Asset Details
Do you wish to reserve the book?
Spermine synthase and MYC cooperate to maintain colorectal cancer cell survival by repressing Bim expression
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
Spermine synthase and MYC cooperate to maintain colorectal cancer cell survival by repressing Bim expression
Do you wish to request the book?
Spermine synthase and MYC cooperate to maintain colorectal cancer cell survival by repressing Bim expression
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Journal Article
Spermine synthase and MYC cooperate to maintain colorectal cancer cell survival by repressing Bim expression
2020
Overview
Dysregulation of polyamine metabolism has been linked to the development of colorectal cancer (CRC), but the underlying mechanism is incompletely characterized. Here, we report that spermine synthase (SMS), a polyamine biosynthetic enzyme, is overexpressed in CRC. Targeted disruption of
SMS
in CRC cells results in spermidine accumulation, which inhibits FOXO3a acetylation and allows subsequent translocation to the nucleus to transcriptionally induce expression of the proapoptotic protein Bim. However, this induction is blunted by MYC-driven expression of miR-19a and miR-19b that repress Bim production. Pharmacological or genetic inhibition of MYC activity in SMS-depleted CRC cells dramatically induces Bim expression and apoptosis and causes tumor regression, but these effects are profoundly attenuated by silencing
Bim
. These findings uncover a key survival signal in CRC through convergent repression of Bim expression by distinct SMS- and MYC-mediated signaling pathways. Thus, combined inhibition of SMS and MYC signaling may be an effective therapy for CRC.
Polyamine metabolism is frequently dysregulated in cancers. Here, the authors show that a polyamine biosynthetic enzyme, spermine synthase, is overexpressed in colorectal cancers and cooperates with MYC to prevent cancer cell apoptosis by repression of proapoptotic protein, Bim.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 13/106
/ 13/109
/ 13/2
/ 13/31
/ 13/44
/ 13/51
/ 13/89
/ 13/95
/ 14/19
/ 38
/ 38/15
/ 38/22
/ 38/23
/ 38/70
/ 38/77
/ 38/88
/ 38/90
/ 45
/ 64/60
/ 82/29
/ 82/80
/ Animals
/ Bcl-2-Like Protein 11 - metabolism
/ Cancer
/ Cell Proliferation - drug effects
/ Cell Survival - drug effects
/ Colorectal Neoplasms - enzymology
/ Colorectal Neoplasms - genetics
/ Colorectal Neoplasms - pathology
/ Down-Regulation - drug effects
/ Enzymes
/ Female
/ Forkhead Box Protein O3 - metabolism
/ Gene Expression Regulation, Neoplastic - drug effects
/ Humanities and Social Sciences
/ Humans
/ Male
/ Proteins
/ Proto-Oncogene Proteins c-myc - metabolism
/ Science
/ Spermine
/ Spermine Synthase - metabolism
/ Survival
