Nature - USA (2020-01-16)

2

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 scRNAseq was performed on three models and 10,177 cells were analyzed. Biosensor experiments analyzed at least 200 cells per condition.

SiRNA experiments, western blotting, viability experiemnts were performed at least twice. Each viability experiement was performed on three

biological replicates. In vivo tumor growth experiments were performed on 4 or 5 biological replicates as indicated.

Data exclusions Single cells were excluded from analysis based on pre-established criteria indicating poor quality of sequencing or doublet reads as indicated

in methods. FACS experiments were gated to analyze only live cells, others were omitted.

Replication The experimental replcates are indicsted in the figure legends. All stated replicates indicate either biological replicates (e.g. viability studies,

tumor growth measurements) or independent experimental repeats (e.g. western blotting, biosensor studies)

Randomization In vivo tumor growth experiments: implanted mice were treated in a random manner with vehicle, single agent or drug combinations.

Otherwise not applicable.

Blinding Tumor growth measurements were carried out in a non blinded manner by a technician not aware of the goals of the experiment. Otherwise

not applicable.

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

Antibodies

Antibodies used These are described in methods.

Validation All antibodies have been validated in our previous publications (KRAS, ERK, pERK, RSK, pRSK, GAPDH, EGFR, pEGFR and CCND1)

or other studies (AURKA, PLK1, CCNB1, RAN and p27).

Eukaryotic cell lines

Policy information about cell lines

Cell line source(s) ATCC

Authentication The cell lines were obtained from ATCC and used withing 20 passages.

Mycoplasma contamination The cell lines used in the study tested negative for mycoplasma.

Commonly misidentified lines

(See ICLAC register)

NA