Yuyin Yi1, Shu-Huei Tsai2, Jung-Chien Cheng3, Evan Y Wang1, Michael S Anglesio4, Dawn R Cochrane5, Megan Fuller6, Ewan A Gibb6, Wei Wei2, David G Huntsman7, Aly Karsan8, Pamela A Hoodless9. 1. Terry Fox Laboratory, BC Cancer Agency, Vancouver, British Columbia V5Z 1L3, Canada; Cell and Developmental Biology Program, University of British Columbia, Vancouver, British Columbia V6T 1Z4, Canada. 2. Terry Fox Laboratory, BC Cancer Agency, Vancouver, British Columbia V5Z 1L3, Canada. 3. Terry Fox Laboratory, BC Cancer Agency, Vancouver, British Columbia V5Z 1L3, Canada; Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia V6T 1Z4, Canada. 4. Department of Gynecology and Obstetrics, University of British Columbia, Vancouver, British Columbia V6Z 2K5, Canada; Department of Molecular Oncology, BC Cancer Agency, Vancouver, British Columbia V5Z 1L3, Canada. 5. Department of Molecular Oncology, BC Cancer Agency, Vancouver, British Columbia V5Z 1L3, Canada. 6. Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia V5Z 4S6, Canada. 7. Department of Gynecology and Obstetrics, University of British Columbia, Vancouver, British Columbia V6Z 2K5, Canada; Department of Molecular Oncology, BC Cancer Agency, Vancouver, British Columbia V5Z 1L3, Canada; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia V6T 2B5, Canada. 8. Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia V5Z 4S6, Canada; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia V6T 2B5, Canada. 9. Terry Fox Laboratory, BC Cancer Agency, Vancouver, British Columbia V5Z 1L3, Canada; Cell and Developmental Biology Program, University of British Columbia, Vancouver, British Columbia V6T 1Z4, Canada; Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia V6T 1Z4, Canada. Electronic address: hoodless@bccrc.ca.
Abstract
OBJECTIVE: APELA is a small, secreted peptide that can function as a ligand for the G-protein coupled receptor, Apelin Receptor (APLNR, APJ). APELA plays an essential role in endoderm differentiation and cardiac development during embryogenesis. We investigated whether APELA exerts any functions in cancer progression. METHODS: The Cancer Genome Atlas (TCGA) RNA sequencing datasets, microarray from an OCCC mouse model, and RNA isolated from fresh frozen and FFPE patient tissue were used to assess APELA expression. APELA knockout ovarian clear cell carcinoma (OCCC) cell lines were generated using CRISPR/Cas9. RESULTS: APELA was expressed in various ovarian cancer histotypes and was especially elevated in OCCC. Disruption of APELA expression in OCCC cell lines suppressed cell growth and migration, and altered cell-cycle progression. Moreover, addition of human recombinant APELA peptide to the OCCC cell line OVISE promoted cell growth and migration. Interestingly, OVISE cells do not express APLNR, suggesting that APELA can function through an APLNR-independent pathway. Furthermore, APELA affected cell growth and cell cycle progression in a p53-dependent manner. In addition, APELA knockdown induced p53 expression in cancer cell lines. CONCLUSIONS: Our findings uncover a potential oncogenic role for APELA in promoting ovarian tumour progression and provide a possible therapeutic strategy in ovarian cancer by targeting APELA.
OBJECTIVE:APELA is a small, secreted peptide that can function as a ligand for the G-protein coupled receptor, Apelin Receptor (APLNR, APJ). APELA plays an essential role in endoderm differentiation and cardiac development during embryogenesis. We investigated whether APELA exerts any functions in cancer progression. METHODS: The Cancer Genome Atlas (TCGA) RNA sequencing datasets, microarray from an OCCC mouse model, and RNA isolated from fresh frozen and FFPE patient tissue were used to assess APELA expression. APELA knockout ovarian clear cell carcinoma (OCCC) cell lines were generated using CRISPR/Cas9. RESULTS:APELA was expressed in various ovarian cancer histotypes and was especially elevated in OCCC. Disruption of APELA expression in OCCC cell lines suppressed cell growth and migration, and altered cell-cycle progression. Moreover, addition of human recombinant APELA peptide to the OCCC cell line OVISE promoted cell growth and migration. Interestingly, OVISE cells do not express APLNR, suggesting that APELA can function through an APLNR-independent pathway. Furthermore, APELA affected cell growth and cell cycle progression in a p53-dependent manner. In addition, APELA knockdown induced p53 expression in cancer cell lines. CONCLUSIONS: Our findings uncover a potential oncogenic role for APELA in promoting ovarian tumour progression and provide a possible therapeutic strategy in ovarian cancer by targeting APELA.
Authors: Shahinda S R Alsayed; Amreena Suri; Anders W Bailey; Samuel Lane; Eryn L Werry; Chiang-Ching Huang; Li-Fang Yu; Michael Kassiou; Simone Treiger Sredni; Hendra Gunosewoyo Journal: RSC Med Chem Date: 2021-08-23
Authors: Cai Read; Duuamene Nyimanu; Thomas L Williams; David J Huggins; Petra Sulentic; Robyn G C Macrae; Peiran Yang; Robert C Glen; Janet J Maguire; Anthony P Davenport Journal: Pharmacol Rev Date: 2019-10 Impact factor: 25.468