Nur77 has a critical role in ovarian cancer progression through the regulation of the TGF-β signaling pathway

The kallikrein-related (KLKs) peptidases are implicated in prostate and ovarian cancer invasion/metastasis via activation of growth factors, proteases and extracellular matrix degradation involved in. In our published work, we used cell biology approaches to show novel associations of KLK peptidases with processes indicative of metastasis and the potential of our novel sunflower trypsin inhibitor scaffold-engineered KLK4 inhibitor. Our current studies are directed towards discovering the precise KLK target proteins/substrates and the subsequent signalling pathways involved in these events in order to determine their therapeutic target potential. In this regard, we are using novel tissue engineered biomimetic 3D gel matrices to better mimic the in vivo micro-environment of prostate cancer cells especially in bone metastasis and peritoneal invasion in ovarian cancer. Pilot studies show that PC3 cells cultured on an osteoblast-derived bone matrix undergo an EMT-like change but remain dispersed on the cell surface. In contrast, LNCaP cells cluster aligning with the fibrillar structure as they invade into the bone matrix as typically seen in vivo. KLK4 proteolysis of the osteoblast-derived bone matrix has identified additional novel substrates. In addition, we are exploring the cell biology that underlies the reported high KLK4 or KLK7 levels associated with poorer outcome in women with epithelial ovarian cancer (EOC). Of note, KLK4 or KLK7 transfected SKOV3 EOC cells have increased chemoresistance to taxol and/or cisplastin suggesting a mechanism for this poor outcome. Furthermore, KLK7 transfected SKOV-3 cells form multicellular aggregates (MCA) in agarose suspension (a process indicative of peritoneal tumour cell spread seen in ascites fluid clinically) which can be reversed by a KLK7 blocking antibody indicating the critical role played by KLK7 in this event. These new paradigms are providing novel information on the role of KLK peptidases in prostate and ovarian cancer progression and their potential as novel therapeutic targets.

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Down-regulation of lncRNA BLACAT1 inhibits ovarian cancer progression by suppressing the Wnt/β-catenin signaling pathway via regulating miR-519d-3p

Molecular and Cellular Biochemistry ◽

10.1007/s11010-020-03704-y ◽

2020 ◽

Vol 467 (1-2) ◽

pp. 95-105 ◽

Cited By ~ 5

Author(s):

Hua Yang ◽

Yue Qi ◽

Xin-lu Wang ◽

Jiao-jiao Gu ◽

Tie-mei Shi

Keyword(s):

Ovarian Cancer ◽

Signaling Pathway ◽

Cancer Progression ◽

Down Regulation

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EPDR1, Which Is Negatively Regulated by miR-429, Suppresses Epithelial Ovarian Cancer Progression via PI3K/AKT Signaling Pathway

Frontiers in Oncology ◽

10.3389/fonc.2021.751567 ◽

2021 ◽

Vol 11 ◽

Author(s):

Zhendan Zhao ◽

Zhiling Wang ◽

Pengling Wang ◽

Shujie Liu ◽

Yingwei Li ◽

...

Keyword(s):

Ovarian Cancer ◽

Epithelial Ovarian Cancer ◽

Signaling Pathway ◽

Cancer Progression ◽

Figo Stage ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Gynecology And Obstetrics

Epithelial ovarian cancer (EOC) is the main pathological type of ovarian cancer. In this study, we found that ependymin-related 1 (EPDR1) was remarkably downregulated in EOC tissues, and low EPDR1 expression was associated with International Federation of Gynecology and Obstetrics (FIGO) stage, metastasis, and poor prognosis. We confirmed that EPDR1 overexpression dramatically suppressed EOC cell proliferation, migration, and invasion in vitro and in vivo. Mechanistically, EPDR1 inhibited EOC tumorigenesis and progression, at least in part, through the repression of the PI3K (Phosphoinositide 3-kinase)/AKT (AKT Serine/Threonine Kinase 1) signaling pathway. Furthermore, the expression and function of EPDR1 were regulated by miR-429, as demonstrated by luciferase reporter assays and rescue experiments. In conclusion, our study validated that EPDR1, negatively regulated by miR-429, played an important role as a tumor-suppressor gene in EOC development via inhibition of the PI3K/AKT pathway. The miR-429/EPDR1 axis might provide novel therapeutic targets for individualized treatment of EOC patients in the future.

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AHNAK suppresses ovarian cancer progression through the Wnt/β-catenin signaling pathway

Aging ◽

10.18632/aging.203473 ◽

2021 ◽

Author(s):

Yanlin Cai ◽

Yi Hu ◽

Furong Yu ◽

Wenjuan Tong ◽

Shufen Wang ◽

...

Keyword(s):

Ovarian Cancer ◽

Signaling Pathway ◽

Cancer Progression

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The Overexpression of Acyl-CoA Medium-Chain Synthetase-3 (ACSM3) Suppresses the Ovarian Cancer Progression via the Inhibition of Integrin β1/AKT Signaling Pathway

Frontiers in Oncology ◽

10.3389/fonc.2021.644840 ◽

2021 ◽

Vol 11 ◽

Author(s):

Limei Yan ◽

Zeping He ◽

Wei Li ◽

Ning Liu ◽

Song Gao

Keyword(s):

Ovarian Cancer ◽

Cell Proliferation ◽

Cell Migration ◽

Signaling Pathway ◽

Cancer Progression ◽

Akt Signaling ◽

Migration And Invasion ◽

Akt Signaling Pathway ◽

Integrin Β1

Ovarian cancer is considered as one of the most fatal gynecologic malignancies. This work aimed to explore the effects and regulatory mechanism of Acyl-CoA medium-chain synthetase-3 (ACSM3, a subunit of CoA ligases) in ovarian cancer progression. As well as employing CCK-8 assay, clone formation assay, and cell cycle analysis were carried out to investigate cell proliferation ability. Wound healing assay and transwell assay were subsequently used to assess cell migration and invasion. Mice xenografts were then conducted to measure the effects of ACSM3 on tumor development in vivo. Our bioinformatics analysis suggested that the expression of ACSM3 was down-regulated in ovarian cancer tissues, and the low expression level of ACSM3 might related with poorer overall survival than high mRNA expression of ACSM3 in ovarian cancer patients. We artificially regulated the expression of ACSM3 to evaluate its effects on ovarian cancer malignant phenotypes. Our data revealed that the overexpression of ACSM3 inhibited cell proliferation, migration, and invasion of ovarian cancer cells. In contrast, the knock-down of ACSM3 received the opposite results. Our western blot results showed that the Integrin β1/AKT signaling pathway was negatively regulated by ACSM3 expression. Moreover, ACSM3 overexpression-induced suppression of cell migration and invasion activities were abolished by the overexpression of ITG β1 (Integrin β1). Additionally, the growth of ovarian cancer xenograft tumors was also repressed by the overexpression of ACSM3. And ACSM3 interference obtained the contrary effects in vivo. In summary, ACSM3 acts as a tumor suppressor gene and may be a potential therapeutic target of ovarian cancer.

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The Intersection of Purine and Mitochondrial Metabolism in Cancer

Cells ◽

10.3390/cells10102603 ◽

2021 ◽

Vol 10 (10) ◽

pp. 2603

Author(s):

Humberto De Vitto ◽

Danushka B. Arachchige ◽

Brian C. Richardson ◽

Jarrod B. French

Keyword(s):

Ovarian Cancer ◽

Cell Growth ◽

Cancer Progression ◽

Critical Role ◽

Building Blocks ◽

Mitochondrial Metabolism ◽

Growth And Survival ◽

Dna And Rna ◽

Purines And Pyrimidines

Nucleotides are essential to cell growth and survival, providing cells with building blocks for DNA and RNA, energy carriers, and cofactors. Mitochondria have a critical role in the production of intracellular ATP and participate in the generation of intermediates necessary for biosynthesis of macromolecules such as purines and pyrimidines. In this review, we highlight the role of purine and mitochondrial metabolism in cancer and how their intersection influences cancer progression, especially in ovarian cancer. Additionally, we address the importance of metabolic rewiring in cancer and how the evolving landscape of purine synthesis and mitochondria inhibitors can be potentially exploited for cancer treatment.

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