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Paclitaxel plus Cirmtuzumab Achieves Greater Clearance of Patient-derived Xenografts By Targeting ROR1+ Breast Cancer Stem Cells

ABSTRACT: Paclitaxel plus Cirmtuzumab Achieves Greater Clearance of Patient-derived Xenografts By Targeting ROR1+ Breast Cancer Stem Cells

PROVIDER: PRJNA427913 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR6430100.fastq.gz	Fastqsanger.gz
	SRR6430101.fastq.gz	Fastqsanger.gz
	SRR6430102.fastq.gz	Fastqsanger.gz
	SRR6430103.fastq.gz	Fastqsanger.gz
	SRR6430104.fastq.gz	Fastqsanger.gz

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Paclitaxel plus Cirmtuzumab Achieves Greater Clearance of Patient-derived Xenografts By Targeting ROR1+ Breast Cancer Stem Cells

Project description:We applied high-throughput sequence to identify signaling pathways, stem cell gene signature or target genes of BMI1 that were affected by our newly development humainzed anti-ROR1 antibody (cirmtuzumab) in breast cancer patient-derived xenograft (PDX) mice model

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TTF-1-induced ROR1 is required to sustain EGFR survival signaling in lung adenocarcinoma

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Project description:We previously reported that ROR1 is a crucial downstream gene for the TTF-1/NKX2-1 lineage-survival oncogene in lung adenocarcinoma, while others have found altered expression of ROR1 in multiple cancer types. Accumulated evidence therefore indicates ROR1 as an attractive molecular target, though it has yet to be determined whether targeting Ror1 can inhibit tumor development and growth in vivo. To this end, genetically engineered mice carrying homozygously floxed Ror1 alleles and an SP-C promoter-driven human mutant EGFR transgene were generated. Ror1 ablation resulted in marked retardation of tumor development and progression in association with reduced malignant characteristics and significantly better survival. Interestingly, gene set enrichment analysis identified a hypoxia-induced gene set (HALLMARK_HYPOXIA) as most significantly downregulated by Ror1 ablation in vivo, which led to findings showing that ROR1 knockdown diminished HIF-1α expression under normoxia and clearly hampered HIF-1α induction in response to hypoxia in human lung adenocarcinoma cell lines. The present results directly demonstrate the importance of Ror1 for in vivo development and progression of lung adenocarcinoma, and also identify Ror1 as a novel regulator of Hif-1α. Thus, a future study aimed at the development of a novel therapeutic targeting ROR1 for treatment of solid tumors such as seen in lung cancer, which are frequently accompanied with a hypoxic tumor microenvironment, is warranted.

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