Nature - 15.08.2019

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nature research | reporting summary

October 2018

Field-specific reporting

Please select the one below that is the best fit for your research. If you are not sure, read the appropriate sections before making your selection.

Life sciences Behavioural & social sciences Ecological, evolutionary & environmental sciences

For a reference copy of the document with all sections, see nature.com/documents/nr-reporting-summary-flat.pdf

Life sciences study design

All studies must disclose on these points even when the disclosure is negative.

Sample size Sample sizes were given in the manuscript. Efficacy studies in mice were conducted with 5 or more mice per group. No statistical methods

were used to predetermine sample size.

Data exclusions No data were excluded.

Replication Replication numbers were reported in the text or in the methodology sections. Where appropriate a measure of the error was reported. All

metabolic tracing and profiling, and cell counting study, were done once. For MTT assay, experiments were repeated at least three times with

similar results. Biological replicates were produced.

Randomization For all animal studies, mice were randomized into different research groups.

Blinding For the dietary studies, the same investigators carried out the dietary treatment and downstream and analysis, so were not

blinded to group allocation.

Reporting for specific materials, systems and methods

We require information from authors about some types of materials, experimental systems and methods used in many studies. Here, indicate whether each material,

system or method listed is relevant to your study. If you are not sure if a list item applies to your research, read the appropriate section before selecting a response.

Materials & experimental systems

n/a Involved in the study

Antibodies

Eukaryotic cell lines

Palaeontology

Animals and other organisms

Human research participants

Clinical data

Methods

n/a Involved in the study

ChIP-seq

Flow cytometry

MRI-based neuroimaging

Eukaryotic cell lines

Policy information about cell lines

Cell line source(s) CRC119 and CRC240 cell lines were developed from their respective CRC PDXs in Dr. David Hsu's lab at Duke University.

HCT116 cell line was a gift from Dr. Lewis Cantley’s laboratory.

Authentication Cell lines were authenticated at the Duke University DNA Analysis Facility by analyzing DNA samples from each cell lines for

polymorphic short tandem repeat (STR) markers using the GenePrint 10 kit from Promega (Madison, WI, USA).

Mycoplasma contamination All cell lines were negative for mycoplasma contamination

Commonly misidentified lines

(See ICLAC register)

No commonly misidentified cell lines were used.

Animals and other organisms

Policy information about studies involving animals; ARRIVE guidelines recommended for reporting animal research

Laboratory animals The following mouse strains were used in the manuscript:

C57BL/6J mice: male, 12-week-old;

NOD.CB17-PrkdcSCID-J mice: male and female, 8-10-week-old;

NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ mice: male and female, 8-10-week-old;

C57BL/6J × 129SvJ mice carrying p53FRT and FSF-KrasG12D: male and female, 6-10-week-old;