Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

CRC micrometastasis generated by AKP MTOs resolved by single cell RNAseq

ABSTRACT: Longitudinal single cell RNA-expression analysis of tumor cells along metastatic relapse. AKP mouse tumor organoids (MTOs) were implanted in the caecum and left to metastasize into the liver. Livers were collected at different timepoints post-injection and GFP+ CD45- cells were sorted in 96-well smart-seq plates. Tumor cells were collected from liver with colorectal cancer (CRC) micrometastatic stage disease.

INSTRUMENT(S): Illumina HiSeq 4000

ORGANISM(S): Mus musculus

SUBMITTER: Eduard Batlle

PROVIDER: E-MTAB-11981 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Metastatic recurrence in colorectal cancer arises from residual EMP1<sup>+</sup> cells.

Cañellas-Socias Adrià A Cortina Carme C Hernando-Momblona Xavier X Palomo-Ponce Sergio S Mulholland Eoghan J EJ Turon Gemma G Mateo Lidia L Conti Sefora S Roman Olga O Sevillano Marta M Slebe Felipe F Stork Diana D Caballé-Mestres Adrià A Berenguer-Llergo Antonio A Álvarez-Varela Adrián A Fenderico Nicola N Novellasdemunt Laura L Jiménez-Gracia Laura L Sipka Tamara T Bardia Lidia L Lorden Patricia P Colombelli Julien J Heyn Holger H Trepat Xavier X Tejpar Sabine S Sancho Elena E Tauriello Daniele V F DVF Leedham Simon S Attolini Camille Stephan-Otto CS Batlle Eduard E

Nature 20221109 7936

Around 30-40% of patients with colorectal cancer (CRC) undergoing curative resection of the primary tumour will develop metastases in the subsequent years<sup>1</sup>. Therapies to prevent disease relapse remain an unmet medical need. Here we uncover the identity and features of the residual tumour cells responsible for CRC relapse. An analysis of single-cell transcriptomes of samples from patients with CRC revealed that the majority of genes associated with a poor prognosis are expressed by a u ...[more]

PMID: 36352230

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Project description:Despite the high prevalence and poor outcome of patients with metastatic lung cancer, the mechanisms of tumour progression and metastasis remain largely uncharacterized. We modelled human lung adenocarcinoma, which frequently harbours activating point mutations in KRAS1 and inactivation of the p53-pathway2, using conditional alleles in mice3-5. Lentiviral-mediated somatic activation of oncogenic Kras and deletion of p53 in the lung epithelial cells of KrasLSL-G12D/+;p53flox/flox mice initiates lung adenocarcinoma development4. Although tumours are initiated synchronously by defined genetic alterations, only a subset become malignant, suggesting that disease progression requires additional alterations. Identification of the lentiviral integration sites allowed us to distinguish metastatic from non-metastatic tumours and determine the gene expression alterations that distinguish these tumour types. Cross-species analysis identified the NK-2 related homeobox transcription factor Nkx2-1 (Ttf-1/Titf1) as a candidate suppressor of malignant progression. In this mouse model, Nkx2-1-negativity is pathognomonic of high-grade poorly differentiated tumours. Gain- and loss-of-function experiments in cells derived from metastatic and non-metastatic tumours demonstrated that Nkx2-1 controls tumour differentiation and limits metastatic potential in vivo. Interrogation of Nkx2-1 regulated genes, analysis of tumours at defined developmental stages, and functional complementation experiments indicate that Nkx2-1 constrains tumours in part by repressing the embryonically-restricted chromatin regulator Hmga2. While focal amplification of NKX2-1 in a fraction of human lung adenocarcinomas has focused attention on its oncogenic function6-9, our data specifically link Nkx2-1 downregulation to loss of differentiation, enhanced tumour seeding ability, and increased metastatic proclivity. Thus, the oncogenic and suppressive functions of Nkx2-1 in the same tumour type substantiate its role as a dual function lineage factor. 23 cell lines derived from primary tumor or metastasis. 6 samples analyzed to determine the effect of Nkx2-1 knockdown on gene expression

Dataset Information

CRC micrometastasis generated by AKP MTOs resolved by single cell RNAseq

Publications

Metastatic recurrence in colorectal cancer arises from residual EMP1<sup>+</sup> cells.

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