the adherent cell lines hek293 ( atcc - crl - 1573 ), hek293t ( atcc - crl - 3216 ) and 293e ( atcc - crl - 10852 ) were obtained from atcc and propagated in dmem ( d6429 ) supplemented with 10 % fbs at 37 °c in a humidified incubator with 5 % co2 in air. suspension cell lines 293 - f, 293 - h and freestyle 293 - f ( gibco ) were obtained from thermo fisher scientific and cultivated in 293 sfm ii medium ( gibco ) supplemented with glutamax at a final concentration of 4 mm ( gibco ). suspension cells were cultivated in 125 - ml erlenmeyer shake flasks ( corning ) at 37 °c and 120 rpm in a humidified incubator with 8 % co2 in air. all cells were propagated from frozen stocks for no longer than 20 passages. adherent cells were detached by trypsinization and both adherent and suspension cells were harvested by centrifugation. genomic dna was extracted using the blood and cell culture dna mini kit ( qiagen ) according to the manufacturer ’ s guidelines and concentrations were determined by using a nanodrop nd - 1000 spectrophotometer ( thermo scientific ). genome sequencing was performed at the national genomics infrastructure ( scilifelab, solna, sweden ) using the illumina hiseq x platform. for rna extraction, cells grown in log phase from three biological replicates were collected ( derived from successive propagations ). cell pellets were resuspended in rnalater stabilization solution ( invitrogen ) according to the manufacturer ’ s recommendations until rna extraction. total rna was extracted from three replicates of each cell line using qiagen ’ s rneasy plus mini kit according to the manufacturer ’ s instructions. concentrations were determined with a nanodrop nd - 1000 spectrophotometer and rna quality was assessed on a 2100 bioanalyzer ( agilent technologies ) using rna 6000 nano chips ( agilent technologies ). all samples had an rna integrity number of at least 9. 9. rna sequencing was performed at gatc ( konstanz, germany ) using the inview transcriptome advance service and an illumina hiseq instrument. genome sequencing reads were aligned to the reference ( human _ g1k _ v37. fasta ) using bwa ( 0. 7. 12 ). the raw alignments were then deduplicated, recalibrated and cleaned using gatk ( version 3. 3 – 0 - geee94ec, gatk - bundle / 2. 8 ). quality control information was gathered using qualimap ( v2. 2 ). snvs and indels have been called using the gatk haplotypecaller. these variants were then functionally annotate d using snpeff ( 4. 1 ) and snpeff reference grch37. 75. the piper pipeline from the national genomics infrastructure was used. the correlation between bam files was assessed using multibamsummary and its plotcorrelation function from deeptools2. spearman was used to calculate correlation coefficients between samples, and the clusters are joined with the nearest neighbor. the r package seqcat was used to compare snvs between samples, its compare _ profiles function mode parameter was set to the default value “ intersection ”. the heatmap in supplementary fig. s1 was based on the similarity scores between the cell lines and euclidean distances. to compare the large t antigen sequences of 293t and 293e, unmapped reads were extracted to new bam files using samtools, converted to fastq with bedtools, and de novo assembled with megahit. ncbi blast was used to identify the large t antigen in the assembled contigs. to evaluate and visualize copy number variations, cnvkit was used with its whole - genome sequencing method, cbs segmentation and the hek293 alignment as reference. go enrichment analysis of genes with high or moderate impact snps was performed using panther classification system. kallisto was used to quantify transcripts by pseudo - alignment based on human genome assembly version grch37. log transformed normalized data by deseq2 was used for cell line clustering and calculation of euclidean distances of samples. the expression comparison of the viral elements was based on normalized counts from deseq2. significant testing of differential mrna expression of e1a / b elements was done by welch two sample t - test. for differential expression analysis, raw count data from kallisto was imported using the tximport package and analyzed with deseq2. wald tests were used to calculate p - values, and the bh method was used for multiple testing correction. throughout the article a gene is considered differentially expressed if log2 - fold change > ± 1 and fdr < 0. 05. in the differential expression analysis between adherent and suspension cells, all suspension cell - lines were compared to all adherent cell - lines, and additionally, all pairwise combinations between suspension and adherent cell - lines were evaluated. for evaluating differential expression of 38 common differentially expressed genes between adherent and suspension hek293 cell lines in a set of 63 human cell lines, rna - seq data from each cell line deposited in the hpa database was used. based on the growth characteristics, cells were divided into two groups of adherent and suspension cells. a mann – whitney u - test was used to compare normalized counts based on library size between the two groups for each of the 38 differentially expressed genes. to discover significant alterations of gene sets and metabolic pathways between hek293 cell lines, the piano package in r was used. the adjusted p - values and fold changes from the differential expression was used in combination with a gene set collection based on “ goslim _ generic biological process ”. the heatmap for the progeny cells lines vs. hek293 was based on the consensus score calculated based on go term rank aggregation in piano for each directionality from all pairwise gene set statistics calculations with wilcoxon rank - sum test. the heatmap for suspension cells ( 293 - h, 293 - f ) vs. adherent cells ( 293e, 293t ) was based on the consensus score from gene set statistics calculations with mean, median, sum, stouffer and tailstrength tests and was calculated with piano ’ s consensusheatmap function. to produce the network plot, gene sets were exported from hmr2. for finding differentially expressed pathways of genes between adherent and suspension cell lines, we used the wilcoxon statistical test and filtered gene sets with adjusted p - value lower than 0. 05 as significantly changed. in addition, for gene set analysis of 38 common de genes between adherent and suspension cell lines we used enrichr and go biological process as gene set collection. in order to predict the pathway changes between cell lines based on differentially expressed genes from pairwise comparisons, ingenuity pathway analysis ( ipa, qiagen inc., ) was performed. to consider a gene as differentially expressed we used log2 fold change > 1 or < 1 and adjusted p - value < 0. 05. for filtering results of gene set analysis by ipa we used benjamini – hochberg multiple testing corrected p - values lower than 0. 05 to find gene sets with a different expression pattern. cancer - associated fibroblasts ( cafs ) are key components of the tumor microenvironment that commonly support cancer development and progression. here we show that different cancer cells transfer mitochondria to fibroblasts in cocultures and xenograft tumors, thereby inducing protumorigenic caf features. transplantation of functional mitochondria from cancer cells induces metabolic alterations in fibroblasts, expression of caf markers and release of a protumorigenic secretome and matrisome. these features promote tumor formation in preclinical mouse models. mechanistically, the mitochondrial transfer requires the mitochondrial trafficking protein miro2. its depletion in cancer cells suppresses mitochondrial transfer and inhibits caf differentiation and tumor growth. the clinical relevance of these findings is reflected by the overexpression of miro2 in tumor cells at the leading edge of epithelial skin cancers.