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Comparison of Prox1 expressing and Prox1 knockout intestinal tumors and the effect of A2V+CD40

ABSTRACT: Comparison of Prox1 expressing and Prox1 knockout intestinal tumors and the effect of A2V+CD40

PROVIDER: PRJNA513202 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR8401480_1.fastq.gz	Fastqsanger.gz
	SRR8401480_2.fastq.gz	Fastqsanger.gz
	SRR8401490_1.fastq.gz	Fastqsanger.gz
	SRR8401490_2.fastq.gz	Fastqsanger.gz
	SRR8401481_1.fastq.gz	Fastqsanger.gz

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Comparison of Prox1 expressing and Prox1 knockout intestinal tumors and the effect of A2V+CD40

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Project description:We isolated and selected intestinal adenoma organoids from Apcmin/+; Rosa26LSL-TdTomato; Prox1-CreERT2 mice. After the selection procedure without growth factors, we induced CreERT2 activity and the transcription of tdTomato to label Prox1+ cells by 300 nM 4-hydroxytamoxifen for 16h. tdTomato+ (Prox1+) and tdTomato- cells (enriched for Prox1- cells) were FACS sorted and total RNA was isolated.

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Project description:Colorectal carcinoma (CRC) progression is associated with an increase in PROX1+ tumor cells, which exhibit features of CRC stem cells and contribute to metastasis. Here, we aimed to provide a better understanding to the function of PROX1+ cells in CRC, investigating their progeny and their role in therapy resistance. PROX1+ cells in intestinal adenomas of ApcMin/+ mice expressed intestinal epithelial and CRC stem cell markers, and cells with high PROX1 expression could both self-renew tumor stem/progenitor cells and contribute to differentiated tumor cells. Most PROX1-lineage traced tumor cells were stem/progenitor cells, which can supply cells to multiple intestinal tumor cell lineages, whereas most lineage-traced LGR5+ tumor cells were enterocytes, indicating that PROX1+ and LGR5+ tumor stem cells have distinct differentiation programs. Although the PROX1+ tumor cells proliferated slower than PROX1- cells, irradiation increased the proportion of PROX1+ cells in human CRC cell lines, patient-derived organoids, and tumor xenografts. Furthermore, transcripts related to DNA damage repair (DDR) were enriched in PROX1+ vs. PROX1- cells in adenomas and in CRC tumor cells from patients. Experiments with PROX1 silencing and overexpression indicated that PROX1 expression enhances CRC cell colony formation following irradiation. PROX1 interacted with DDR proteins, including components of non-homologous end-joining (NHEJ) and base excision repair, and inhibition of NHEJ repair led to a decreased proportion of PROX1+ cells following irradiation. In conclusion, PROX1+ cells are irradiation-resistant tumor stem/progenitor cells capable of self-renewal and differentiation. DDR inhibitors could represent a strategy to target the treatment-resistant PROX1+ tumor stem cells.

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Cd40

Project description:Rattus norvegicus Cd40, CD40 molecule [Source:RGD Symbol;Acc:619830], is expressed in 4 baseline experiment(s);

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Project description:Sus scrofa CD40, CD40 molecule [Source:VGNC Symbol;Acc:VGNC:95545], is expressed in 3 baseline experiment(s);

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