Summary of Study ST000077

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR000055. The data can be accessed directly via it's Project DOI: 10.21228/M83S3W This work is supported by NIH grant, U2C- DK119886.

See: https://www.metabolomicsworkbench.org/about/howtocite.php

Perform statistical analysis  |  Show all samples  |  Show named metabolites  |  Download named metabolite data  
Download mwTab file (text)   |  Download mwTab file(JSON)   |  Download data files (Contains raw data)
Study IDST000077
Study TitleMetabolite changes associated with methionine stress sensitivity of cancer (CSH QTOF MS analysis)
Study Typetimecourse study
Study SummaryThis West Coast Metabolomics Center pilot and feasibility project granted to Peter Kaiser (UC Irvine), aims to achieve understanding of a unique metabolic dependence of cancer cells to explore development of novel unconventional therapeutic strategies that exploit dependence of cancer cells on methyl-donor abundance. The past few years have highlighted the role of altered metabolism in cancer. While mechanistic insight into changed metabolism in cancer is very limited, the importance of the metabolic pathway surrounding homocysteine and methionine for cancer cell proliferation has been known for over 30 years. These findings, generally summarized as methionine-dependence or methionine stress sensitivity, describe the phenomenon that most cancer cells cannot proliferate in growth medium where the amino acid methionine is replaced with its direct metabolic precursor homocysteine. Importantly, non-tumorigenic cells are unaffected by replacing methionine with homocysteine in the growth medium. For the past years we have been studying methionine dependence of breast and prostate cancer and demonstrated that methionine-dependence is caused by insufficient flux through this pathway to sustain synthesis of the downstream metabolite and the principal methyl-donor S-adenosylmethionine (SAM). We have isolated rare cell clones from MDA-MB468 breast cancer cells (referred to as MB468RES) that are no longer methionine dependent and proliferate in homocysteine medium. Interestingly, MB468RES have lost their ability for anchorage independent growth, a hallmark of cancer. The MB468 and MB468RES cell line pair confirms other observations showing that methionine dependence is tightly linked to tumorigenicity. Importantly, this cell line pair is an ideal model to identify metabolite signatures linked to cancer cell methionine dependence. We propose to characterize the metabolic changes triggered by the shift from normal growth medium to homocysteine medium in MB468 breast cancer cells and the methionine stress insensitive MB468RES derivatives. In addition we have developed cancer cell lines with inducible shRNAs targeting methionine adenosyltransferase (MAT), the enzyme catalyzing synthesis of SAM from methionine and ATP. Inducible knockdown of MAT allows us to specifically reduce SAM synthesis. Our previous results suggest that SAM limitation is the critical trigger for cancer cell methionine dependence. Thus metabolite profiling using the MAT knockdown system will provide an independent dataset that together with metabolite profiles from the MB468 and MB468RES cell line pair will define critical metabolic profiles related to cancer cell methionine dependence.   In the current investigation, untargeted analysis of primary metabolites and complex lipids, coupled with quantitative analysis of methionine pathway intermediates (folate and respective derivatives, s-adenosylmethoinine, s-adenosylhomocysteine, choline, betaine) and metabolic flux will be conducted on MB468, MB468RES and MB468shRNA following the switch from methionine containing media to homocysteine containing media over the course of 0, 2, 4, 8, 12, 24 and 48 hours.   The primary objectives were to 1) characterize the metabolic response to methionine stress and SAM limitation and 2) correlate the metabolic signatures with cancer cell proliferation arrest and death. 
Institute
University of California, Davis
DepartmentGenome and Biomedical Sciences Facility
LaboratoryWCMC Metabolomics Core
Last NameFiehn
First NameOliver
Address1315 Genome and Biomedical Sciences Facility 451 Health Sciences Drive Davis, CA 95616
Emailofiehn@ucdavis.edu
Phone(530) 754-8258
Submit Date2014-06-11
Num Groups2
Total Subjects71
Study CommentsLipidomics profiles for study
Raw Data AvailableYes
Raw Data File Type(s)d
Uploaded File Size11 G
Analysis Type DetailLC-MS
Release Date2014-07-24
Release Version1
Oliver Fiehn Oliver Fiehn
https://dx.doi.org/10.21228/M83S3W
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

Select appropriate tab below to view additional metadata details:


Factors:

Subject type: Human cells; Subject species: Homo sapiens (Factor headings shown in green)

mb_sample_id local_sample_id Treatment Timepoint
SA003967CSH_sample_1-2_100uM Met _0 hours_1132014.d100uM Met 0 hours
SA003968CSH_sample_3-2_100uM Met _0 hours_1132014.d100uM Met 0 hours
SA003969CSH_sample_4-2_100uM Met _0 hours_1132014.d100uM Met 0 hours
SA003970CSH_sample_2-2_100uM Met _0 hours_1132014.d100uM Met 0 hours
SA003971CSH_sample_2-2_370uM Hcy _12 hours_1132014.d370uM Hcy 12 hours
SA003972CSH_sample_3-2_370uM Hcy _12 hours_1132014.d370uM Hcy 12 hours
SA003973CSH_sample_4-2_370uM Hcy _12 hours_1132014.d370uM Hcy 12 hours
SA003974CSH_sample_1-2_370uM Hcy _12 hours_1132014.d370uM Hcy 12 hours
SA003979CSH_sample_4-2_370uM Hcy _24 hours_1132014.d370uM Hcy 24 hours
SA003980CSH_sample_2-2_370uM Hcy _24 hours_1132014.d370uM Hcy 24 hours
SA003981CSH_sample_1-2_370uM Hcy _24 hours_1132014.d370uM Hcy 24 hours
SA003982CSH_sample_3-2_370uM Hcy _24 hours_1132014.d370uM Hcy 24 hours
SA003975CSH_sample_4-2_370uM Hcy _2 hours_1132014.d370uM Hcy 2 hours
SA003976CSH_sample_2-2_370uM Hcy _2 hours_1132014.d370uM Hcy 2 hours
SA003977CSH_sample_1-2_370uM Hcy _2 hours_1132014.d370uM Hcy 2 hours
SA003978CSH_sample_3-2_370uM Hcy _2 hours_1132014.d370uM Hcy 2 hours
SA003987CSH_sample_1-2_370uM Hcy _48 hours_1132014.d370uM Hcy 48 hours
SA003988CSH_sample_4-2_370uM Hcy _48 hours_1132014.d370uM Hcy 48 hours
SA003989CSH_sample_2-2_370uM Hcy _48 hours_1132014.d370uM Hcy 48 hours
SA003990CSH_sample_3-2_370uM Hcy _48 hours_1132014.d370uM Hcy 48 hours
SA003983CSH_sample_4-2_370uM Hcy _4 hours_1132014.d370uM Hcy 4 hours
SA003984CSH_sample_1-2_370uM Hcy _4 hours_1132014.d370uM Hcy 4 hours
SA003985CSH_sample_2-2_370uM Hcy _4 hours_1132014.d370uM Hcy 4 hours
SA003986CSH_sample_3-2_370uM Hcy _4 hours_1132014.d370uM Hcy 4 hours
SA003991CSH_sample_3-2_370uM Hcy _8 hours_1132014.d370uM Hcy 8 hours
SA003992CSH_sample_2-2_370uM Hcy _8 hours_1132014.d370uM Hcy 8 hours
SA003993CSH_sample_1-2_370uM Hcy _8 hours_1132014.d370uM Hcy 8 hours
SA003994CSH_BioRec_Plasma_03_1132014.dquality check quality check
SA003995CSH_BioRec_Plasma_01_1132014.dquality check quality check
SA003996CSH_BioRec_Plasma_02_1132014.dquality check quality check
Showing results 1 to 30 of 30
  logo