Targeting FAPα-positive lymph node metastatic tumor cells suppresses colorectal cancer metastasis

Lymphatic metastasis is the main metastatic route for colorectal cancer, which increases the risk of cancer recurrence and distant metastasis. The properties of the lymph node metastatic colorectal cancer (LNM-CRC) cells are poorly understood, and effective therapies are still lacking. Here, we found that hypoxia-induced fibroblast activation protein alpha (FAPα) expression in LNM-CRC cells. Gain- or loss-function experiments demonstrated that FAPα enhanced tumor cell migration, invasion, epithelial-mesenchymal transition, stemness, and lymphangiogenesis via activation of the STAT3 pathway. In addition, FAPα in tumor cells induced extracellular matrix remodeling and established an immunosuppressive environment via recruiting regulatory T cells, to promote colorectal cancer lymph node metastasis (CRCLNM). Z-GP-DAVLBH, a FAPα-activated prodrug, inhibited CRCLNM by targeting FAPα-positive LNM-CRC cells. Our study highlights the role of FAPα in tumor cells in CRCLNM and provides a potential therapeutic target and promising strategy for CRCLNM.

Transcriptome profiles of pre-pubertal and adult in vitro matured ovine oocytes obtained from FSH-stimulated animals.

Pre-pubertal females produce more oocytes than adult individuals, but the ability of oocytes to undergo embryonic development and produce viable offspring is less in pre-pubertal animals than in adult animals. Oocyte quality is associated with abnormal gene expression. To date, the transcriptome profiles of 1-month-old lamb oocytes after in vitro maturation (IVM) are poorly reported. This study aimed to identify differentially expressed genes (DEGs) in lamb oocytes with varying competencies, affecting oocyte competence. Using RNA sequencing (RNA developmental -seq) technology, the transcriptome profiles of 1-month-old lamb oocytes after IVM were assessed, and oocytes from adult sheep large follicles were used as controls. We found 11 up-regulated and 39 down-regulated DEGs in lamb oocytes. Gene Ontology analysis of DEGs showed that molecular functions were clustered in catalytic and binding activities, while biological processes were clustered in metabolic process, cellular process, single-organism process and biological regulation. Kyoto Encyclopedia of Genes and Genomes analysis showed that the DEGs were involved in oxidative phosphorylation, transforming growth factor-beta signalling pathway, or DNA replication. In lamb MII oocytes, down-regulation of oxidative phosphorylation genes (ATP5E, NDUFA7 and COX6C), thiol protease inhibitor (CSTB) and 26S proteasome component (SHFM1) and up-regulation of CUL1, MARCH7 and TRIM17 might cause low competence of lamb embryos. In conclusion, this study provided detailed information on mRNA transcriptomes in lamb oocytes after IVM, which offers insights into the reduced developmental potential of lamb oocytes.