E-resources
-
Liu, Xiaojing; Romero, Iris L.; Litchfield, Lacey M.; Lengyel, Ernst; Locasale, Jason W.
Cell metabolism, 11/2016, Volume: 24, Issue: 5Journal Article
Repurposing metformin for cancer therapy is attractive due to its safety profile, epidemiological evidence, and encouraging data from human clinical trials. Although it is known to systemically affect glucose metabolism in liver, muscle, gut, and other tissues, the molecular determinants that predict a patient response in cancer remain unknown. Here, we carry out an integrative metabolomics analysis of metformin action in ovarian cancer. Metformin accumulated in patient biopsies, and pathways involving nucleotide metabolism, redox, and energy status, all related to mitochondrial metabolism, were affected in treated tumors. Strikingly, a metabolic signature obtained from a patient with an exceptional clinical outcome mirrored that of a responsive animal tumor. Mechanistically, we demonstrate with stable isotope tracing that these metabolic signatures are due to an inability to adapt nutrient utilization in the mitochondria. This analysis provides new insights into mitochondrial metabolism and may lead to more precise indications of metformin in cancer. Display omitted •Metformin accumulates in human tumor biopsies at micromolar concentrations•The response to metformin in humans can be modeled in nutrient-limited environments•Mitochondrial substrate utilization underlies metformin sensitivity•Restoration of specific mitochondrial outputs causes resistance to metformin Liu et al. carry out an integrative metabolomics analysis of metformin action in ovarian cancer. Using patient samples (including those from a “super-responder”), animal tumors, and cell culture models, they find that the predominant mechanism of action by metformin in cancer is to target tumor-cell-intrinsic mitochondrial metabolism.
![loading ... loading ...](themes/default/img/ajax-loading.gif)
Shelf entry
Permalink
- URL:
Impact factor
Access to the JCR database is permitted only to users from Slovenia. Your current IP address is not on the list of IP addresses with access permission, and authentication with the relevant AAI accout is required.
Year | Impact factor | Edition | Category | Classification | ||||
---|---|---|---|---|---|---|---|---|
JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
Select the library membership card:
If the library membership card is not in the list,
add a new one.
DRS, in which the journal is indexed
Database name | Field | Year |
---|
Links to authors' personal bibliographies | Links to information on researchers in the SICRIS system |
---|
Source: Personal bibliographies
and: SICRIS
The material is available in full text. If you wish to order the material anyway, click the Continue button.