Fig. 1

TTC17 deficiency is identified as a metastasis driver in breast cancer via high-throughput omics screening. a Flowchart of all screening processes involved in the study. b Schematic representation of loss-of-function screening for metastasis-related genes using the human genome-scale CRISPR–Cas9 knockout library linked to Transwell invasion assays. c Identification of top genes as candidates concerning their invasion-promoting ability in Transwell screening with MCF7 breast cancer cells using MAGeCK analysis. The red line indicates a P value of 0.05. d, e GO (d) and KEGG (e) enrichment for candidate genes identified by GeCKOv.2 library screening in Fig. 1b and c. f Overlap of differentially mutated genes between metastatic and nonmetastatic breast cancer from a genomic data comparison in the TCGA database and whole-exome sequencing of tissue samples from our patient cohort. g Kaplan‒Meier survival plots of relapse-free survival in breast cancer patients with distinct TTC17 transcriptional expression. h Heatmap of representative genes screened by random forest analysis using the transcriptomic data of metastatic and nonmetastatic breast cancer cases from TCGA with low expression promoting metastasis. i, j Schematic illustration (i) and enrichment of candidate genes (j) for a 64-gene CRISPR screening library using in vivo lung metastasis models of MDA-MB-231 breast cancer cells. CRISPR, clustered regularly interspaced short palindromic repeats; WES, whole-exome sequencing; TCGA, the Cancer Genome Atlas; DMGs, differentially mutated genes; RFS, relapse-free survival; KM, Kaplan–Meier; GO, Gene Ontology; KEGG, Kyoto Encyclopedia of Genes and Genomes; GeCKO, genome-scale CRISPR–Cas9 knockout