The Role of MUC16 Mucin (CA125) in the Pathogenesis of Ovarian Cancer

Rancourt, Claudine; Matte, Isabelle; Lane, Denis; Piché, Alain

doi:10.5772/27672

Cited by 5 publications

(6 citation statements)

References 105 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…MUC16 down-regulates TRAIL-R2 and up-regulates cFLIP expression both resulting in the inhibition of caspase-8 activation at the DISC. The basis for this discrepancy in term of mechanisms between MUC1 and MUC16 is unclear but may relate to the fact that different cellular models were used or, more likely, to the fact that MUC1 and MUC16 share very little sequence homology in their cytoplasmic tail [ 41 ]. MUC16 has a very short intracellular domain (31 a.a.) compared to MUC1 (72 a.a.).…”

Section: Discussionmentioning

confidence: 99%

MUC16 mucin (CA125) attenuates TRAIL-induced apoptosis by decreasing TRAIL receptor R2 expression and increasing c-FLIP expression

et al. 2014

Self Cite

View full text Add to dashboard Cite

BackgroundMUC16 (CA125) is a large transmembrane mucin protein (> 200 kDa) aberrantly expressed in approximately 80% of human epithelial ovarian cancers (EOC). MUC16 expression in EOC cells is associated with increased tumorigenesis and inhibiton of genotoxic drug-induced apoptosis. However, the mechanism by which MUC16 mediates these effects is unknown. In the present study, we investigated the mechanisms by which MUC16 attenuates TRAIL-induced apoptosis.MethodsMUC16 expression was down-regulated by stably expressing an anti-MUC16 single-chain antibody (scFv) targeted to the endoplasmic reticulum (ER), which prevents cell surface localization of MUC16 in OVCAR3 cells. We also generated a MUC16 C-terminal domain (MUC16CTD) construct that was stably expressed in MUC16 negative SKOV3 cells.ResultsWe show that MUC16 attenuates apoptosis, activation of caspase-8 and mitochondria activation in EOC cells in response to TRAIL. MUC16 decreases TRAIL receptor R2 (DR5) expression and inhibits pro-caspase-8 activation at the death-inducing signaling complex (DISC). MUC16CTD expression is sufficient to attenuate the TRAIL signaling cascade. MUC16 knockdown decreases caspase-8 inhibitor cFLIP mRNA levels, increases cFLIP degradation, and consequently increases TRAIL-induced apoptosis. Down-regulation of cFLIP following treatment of MUC16-expressing OVCAR3 cells with cFLIP siRNA also increases TRAIL-induced apoptosis.ConclusionsThese findings indicate that MUC16 protects EOC cells against TRAIL-induced apoptosis through multiple mechanisms including the blockade of TRAIL R2 expression and the regulation of cFLIP expression at both the transcriptional and the protein level.

show abstract

Section: Discussionmentioning

confidence: 99%

MUC16 mucin (CA125) attenuates TRAIL-induced apoptosis by decreasing TRAIL receptor R2 expression and increasing c-FLIP expression

et al. 2014

Self Cite

View full text Add to dashboard Cite

show abstract

“…Dilaporkan bahwa peningkatan dua kali lipat kadar CA-125 paska pemberian kemoterapi berkaitan erat dengan kekambuhan kanker ovarium dengan sensitivitas 86%, spesifitas 91%, NPP 95% dan NPN 78%. 19 Beberapa penelitian dilakukan untuk menilai sensitivitas skor PCI terhadap resektabilitas dan kelangsungan hidup pasien kanker ovarium. Nilai cut-off skor PCI yang berbeda-beda telah digunakan dalam beberapa penelitian, nilai cut-off skor PCI rata-rata yang digunakan adalah 10-15.…”

Section: 8unclassified

Hubungan Nilai PCI Intraoperatif dengan Resektabilitas Kanker Ovarium di RSUP Dr. M. Djamil Padang

Muhammad,

Fajriman

2023

Obgynia

View full text Add to dashboard Cite

Ukuran luas massa sebelum operasi berperan dalam keberhasilan sitoreduksi komplit. Peritonial Carcinomatosis Index (PCI) adalah sistem yang paling umum digunakan untuk peritoneal carcinomatosis, dan indikator prognostik independen untuk hasil jangka panjang. Resektabilitas kanker ovarium ditandai dengan residu kanker berpengaruh terhadap prognosis. Penggunaan PCI pada kanker ovarium sebagai faktor prediktor resektabilitas akan meniadakan sebagian faktor perancu terkait tim bedah. Penelitian ini bertujuan mengetahui hubungan nilai PCI metastasis intraoperatif terhadap resektabilitas massa pada kanker ovarium stadium lanjut di RSUP Dr. M. Djamil Padang. Metode: Penelitian analitik observasional dengan desain cross sectional study. Kriteria inklusi berupa pasien kanker ovarium stadium lanjut 1C yang akan dilakukan operasi dan bersedia menandatangani informed consent sejak Oktober 2021. Hasil: Sebanyak 52.5% memiliki riwayat genetik, 72.5% berusia 40 -70 tahun. Pasien rawatan kanker ovarium stadium lanjut di RSUP Dr. M. Djamil Padang sebanyak 95% IOTA SR malignant, sebanyak 100% memiliki nilai CA-125 >35, 60% ukuran massa >1 cm. PCI tinggi (skor >15-39) memiliki frekuensi lebih tinggi dibandingkan nilai PCI Rendah (62,5%). Persentase resektabel lebih tinggi pada nilai PCI rendah dibandingkan nilai PCI tinggi sebanyak 100% (<0.001). Kesimpulan : Terdapat hubungan signifikan antara nilai Peritoneal Carcinomatosis Index intraoperatif dan resektabilitas massa.

show abstract

“…8,9 Observations also suggest that, in patients with heart disease, CA125 may be used as a risk stratification tool because particularly high levels have been linked to rehospitalisation and death. 8 Figure 2 summarises the physiological and pathological causes of raised CA125 levels.…”

Section: Ca125 and Benign Conditionsmentioning

confidence: 99%

“…CA125 levels have been shown to be elevated in various benign conditions, including gynaecological pathologies such as benign ovarian cysts, tubo‐ovarian abscess, endometriosis, pelvic inflammatory disease, fibroids and ovarian hyperstimulation syndrome 26 . Many nongynaecological conditions are also associated with markedly elevated CA125 levels, including liver cirrhosis; 13 lung diseases like interstitial lung disease and tuberculosis; 36 and heart diseases such as heart failure, atrial fibrillation and pericardial disease 8,9 . Observations also suggest that, in patients with heart disease, CA125 may be used as a risk stratification tool because particularly high levels have been linked to rehospitalisation and death 8 …”

Section: Raised Ca125 Without Ovarian Cancermentioning

confidence: 99%

See 1 more Smart Citation

Raised CA125 – what we actually know…

Howe

Sokolovsky

Sayasneh

et al. 2020

The Obstetric & Gynaecologis

View full text Add to dashboard Cite

Carbohydrate antigen 125 (CA125) is an antigen used in the diagnosis of epithelial nonmucinous ovarian cancers. CA125 may be elevated in many benign and malignant conditions, so elevated levels can cause confusion over patient management. The multidisciplinary team is important when planning care for patients with suspected ovarian cancer. Learning objectivesTo know the factors leading to CA125 production and its mechanism of action.To understand how CA125 is used as a diagnostic tool and to assess the treatment response of ovarian cancer. To appreciate patient care options in cases of falsely elevated CA125. Ethical issuesIs the CA125 blood test being used in patients appropriately and safely? In patients with elevated CA125 levels, does this lead to unnecessary investigations and invasive treatments? Keywords: CA125 / gynaecological causes of raised CA125 / nongynaecological causes of raised CA125 / ovarian cancer / ovarian cancer follow-up

show abstract

The Role of MUC16 Mucin (CA125) in the Pathogenesis of Ovarian Cancer

Cited by 5 publications

References 105 publications

MUC16 mucin (CA125) attenuates TRAIL-induced apoptosis by decreasing TRAIL receptor R2 expression and increasing c-FLIP expression

MUC16 mucin (CA125) attenuates TRAIL-induced apoptosis by decreasing TRAIL receptor R2 expression and increasing c-FLIP expression

Hubungan Nilai PCI Intraoperatif dengan Resektabilitas Kanker Ovarium di RSUP Dr. M. Djamil Padang

Raised CA125 – what we actually know…

Contact Info

Product

Resources

About