Centrosomal Protein 55 (CEP55) exhibits various oncogenic activities; it regulates the PI3K-Akt-pathway, midbody abscission, and chromosomal instability (CIN) in cancer cells. Here, we analyzed the mechanism of how CEP55 controls CIN in ovarian and breast cancer (OvCa) cells. Down-regulation of CEP55 reduced CIN in all cell lines analyzed, and CEP55 depletion decreased spindle microtubule (MT)-stability in OvCa cells. Moreover, recombinant CEP55 accelerated MT-polymerization and attenuated cold-induced MT-depolymerization. To analyze a potential relationship between CEP55-controlled CIN and its impact on MT-stability, we identified the CEP55 MT-binding peptides inside the CEP55 protein. Thereafter, a mutant with deficient MT-binding activity was re-expressed in CEP55-depleted OvCa cells and we could show that this mutant did not restore reduced CIN in CEP55-depleted cells. This finding strongly indicates that CEP55 regulates CIN by controlling MT dynamics.
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http://dx.doi.org/10.3390/cells13161382 | DOI Listing |
Front Immunol
January 2025
Leeds Institute of Medical Research, School of Medicine, University of Leeds, St. James University Hospital, Leeds, United Kingdom.
Background: There has been limited success of cancer immunotherapies in the treatment of ovarian cancer (OvCa) to date, largely due to the immunosuppressive tumour microenvironment (TME). Tumour-associated macrophages (TAMs) are a major component of both the primary tumour and malignant ascites, promoting tumour growth, angiogenesis, metastasis, chemotherapy resistance and immunosuppression. Differential microRNA (miRNA) profiles have been implicated in the plasticity of TAMs.
View Article and Find Full Text PDFJ Cell Mol Med
December 2024
Department of Gynecology, School of Medicine, Shanghai First Maternity and Infant Hospital, Tongji University, Shanghai, China.
Ovarian cancer (OvCa) is the most lethal gynaecology malignancies worldwide. Neutrophil extracellular traps (NETs), net-like protein structures produced by activated neutrophils and DNA-histone complexes, have a central role in tumours, though haven't been fully explored in OvCa. We obtained transcriptome data from TCGA-OvCa database (n = 376) as training, ICGC-OvCa database (n = 111) as validation and GTEx database (n = 180) as controls.
View Article and Find Full Text PDFCell Commun Signal
December 2024
Departmentof Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Background: Peritoneal dissemination of ovarian cancer (OvCa) can be largely attributed to the formation of a metastatic microenvironment driven by tumoral exosomes. Here, we aimed to elucidate the mechanisms through which exosomal annexin A2 (ANXA2) derived from OvCa cells induces an HPMC phenotypic shift in favour of peritoneal metastasis.
Methods: Immunohistochemistry and orthotopic and intraperitoneal OvCa xenograft mouse models were used to clarify the relationship between tumour ANXA2 expression and peritoneal metastasis.
Cells
November 2024
Women's Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health (NIH), Bethesda, MD 20892, USA.
Poly (ADP-ribose) polymerase inhibitors (PARPis) show cytotoxicity in homologous recombination deficiency (HRD) seen in -mutant ovarian cancer (OvCa). Despite initial responses, resistance often develops. The reintroduction of different PARPis, such as niraparib or rucaparib, has shown some clinical activity in mutation-associated OvCa patients with prior olaparib treatment, yet the underlying mechanisms remain unclear.
View Article and Find Full Text PDFJ Exp Med
December 2024
Immunology, Microenvironment and Metastasis Program, Ellen and Ronald Caplan Cancer Center, The Wistar Institute, Philadelphia, PA, USA.
Patients with metastatic ovarian cancer (OvCa) have a 5-year survival rate of <30% due to the persisting dissemination of chemoresistant cells in the peritoneal fluid and the immunosuppressive microenvironment in the peritoneal cavity. Here, we report that intraperitoneal administration of β-glucan and IFNγ (BI) induced robust tumor regression in clinically relevant models of metastatic OvCa. BI induced tumor regression by controlling fluid tumor burden and activating localized antitumor immunity.
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