- PDCD4 suppresses proliferation, migration and invasion of endometrial cells by inhibiting autophagy and NF-κB/MMP2/MMP9 signal pathway. [Journal Article]
- BRBiol Reprod 2018 Jun 15
- Endometriosis (EM) is a kind of estrogen-dependent disease in reproductive-age women. Ovarian endometriosis is the most common type. Although endometriosis is a benign disease, it shares many similar...
Endometriosis (EM) is a kind of estrogen-dependent disease in reproductive-age women. Ovarian endometriosis is the most common type. Although endometriosis is a benign disease, it shares many similar features with cancers. Programmed cell death 4 (PDCD4), a newly identified tumor suppressor, plays an important role in inhibiting tumorigenesis and tumor progression at the transcriptional and translational levels. To explore the roles of PDCD4 in endometriosis, we detected the expression of PDCD4 in control endometrium and eutopic/ectopic endometrium of ovarian endometriosis patients, and analyzed the effects of PDCD4 on the biological behaviors of endometrial cell lines and primary endometrial cells. The results demonstrated that PDCD4 was downregulated in eutopic and ectopic endometrium of endometriosis patients compared with control endometrium. PDCD4 effectively inhibited the proliferation and colony-forming ability of endometrial cells maybe by inhibiting cell autophagy. In addition, PDCD4 also suppressed the migration and invasion ability of endometrial cells, the mechanism may be related to NF-κB/MMP2/MMP9 signal pathway. Taken together, these results suggest PDCD4 could be involved in the pathogenesis of endometriosis, and provide a novel approach to target the aberrant PDCD4 expression in endometriosis.programmed cell death 4 (PDCD4), endometriosis, proliferation, migration, invasion.
- Targeting Tumor-Associated Exosomes with Integrin-Binding Peptides. [Journal Article]
- ABAdv Biosyst 2017; 1(5)
- All cells expel a variety of nano-sized extracellular vesicles (EVs), including exosomes, with composition reflecting the cells' biological state. Cancer pathology is dramatically mediated by EV traf...
All cells expel a variety of nano-sized extracellular vesicles (EVs), including exosomes, with composition reflecting the cells' biological state. Cancer pathology is dramatically mediated by EV trafficking via key proteins, lipids, metabolites, and microRNAs. Recent proteomics evidence suggests that tumor-associated exosomes exhibit distinct expression of certain membrane proteins, rendering those proteins as attractive targets for diagnostic or therapeutic application. Yet, it is not currently feasible to distinguish circulating EVs in complex biofluids according to their tissue of origin or state of disease. Here we demonstrate peptide binding to tumor-associated EVs via overexpressed membrane protein. We find that SKOV-3 ovarian tumor cells and their released EVs express α3β1 integrin, which can be targeted by our in-house cyclic nonapeptide, LXY30. After measuring bulk SKOV-3 EV association with LXY30 by flow cytometry, Raman spectral analysis of laser-trapped single exosomes with LXY30-dialkyne conjugate enabled us to differentiate cancer-associated exosomes from non-cancer exosomes. Furthermore, we introduce the foundation for a highly specific detection platform for tumor-EVs in solution with biosensor surface-immobilized LXY30. LXY30 not only exhibits high specificity and affinity to α3β1 integrin-expressing EVs, but also reduces EV uptake into SKOV-3 parent cells, demonstrating the possibility for therapeutic application.
- A panel of three oxidative stress-related genes predicts overall survival in ovarian cancer patients received platinum-based chemotherapy. [Journal Article]
- AAging (Albany NY) 2018 Jun 17
- Ovarian cancer yields the highest mortality rate of all lethal gynecologic cancers, and the prognosis is unsatisfactory with the major obstacle in resistance to chemotherapy. The generation of reacti...
Ovarian cancer yields the highest mortality rate of all lethal gynecologic cancers, and the prognosis is unsatisfactory with the major obstacle in resistance to chemotherapy. The generation of reactive oxygen species (ROS) in tumor tissues was associated with chemotherapeutic effectiveness by mediating cellular longevity. In this study, we screened the prognostic values of oxidative stress-related genes in ovarian cancer patients received platinum-based chemotherapy, and conducted a prognostic gene signature composing of three genes, TXNRD1, GLA and GSTZ1. This three-gene signature was significantly associated with overall survival (OS), but not progression-free survival (PFS), in both training (n=276) and validation cohorts (n=230). Interestingly, we found that the prognostic value of three-gene signature was reinforced in platinum-sensitive patients. Subgroup analysis further suggested that patients with elder age, higher pathological grades and advanced tumor stages in low-risk score group could benefit from platinum-based chemotherapy. Functional analysis showed that the inactivation of several signaling pathways, including cell cycle, insulin-like growth factor 1 (IGF1) /mTOR and Fas pathways, was affected by three genes. Collectively, our results provided evidence that a panel of three oxidative stress-related gene signature had prognostic values for ovarian cancer patients received platinum-based chemotherapy.
- Prucalopride Inhibits Proliferation of Ovarian Cancer Cells via Phosphatidylinositol 3-Kinase (PI3K) Signaling Pathway. [Journal Article]
- MSMed Sci Monit 2018 Jun 17; 24:4137-4145
- CONCLUSIONS: The present study reveals that in ovarian cancer cells, prucalopride inhibits proliferation, migration, and invasion, and induces apoptosis and autophagy, which may be regulated by the PI3K signaling pathway. These results suggest prucalopride has potential as a new drug for clinical ovarian cancer treatment.
- Correction: Ubiquitous Release of Exosomal Tumor Suppressor miR-6126 from Ovarian Cancer Cells. [Journal Article]
- CRCancer Res 2018 Jun 15; 78(12):3402
- Degradation of DAXX by adenovirus type 12 E1B-55K circumvents chemoresistance of ovarian cancer to cisplatin. [Journal Article]
- VVirology 2018 Jun 12; 521:118-128
- Adenovirus E1B 55-kilodalton (E1B-55K) mediated DAXX degradation represents a potential mechanism by which E1B-55K sensitizes cancer cells to chemotherapy. Here we report the effects of E1B-55K-media...
Adenovirus E1B 55-kilodalton (E1B-55K) mediated DAXX degradation represents a potential mechanism by which E1B-55K sensitizes cancer cells to chemotherapy. Here we report the effects of E1B-55K-mediated DAXX degradation in chemoresistant ovarian cancer cells on response to chemotherapy. Cells with E1B-55K expression were more sensitive to cisplatin than cells without E1B-55K expression. In vivo C13* xenograft studies showed that the combination of cisplatin and E1B-55K was markedly more effective to slow tumor growth and to confer prolonged survival of tumor-bearing mice than either cisplatin or E1B-55K alone. Our studies show that DAXX plays an important role in cisplatin resistance in ovarian cancer, and strategies that promote DAXX degradation such as E1B-55K expression in combination with cisplatin can overcome drug resistance and improve responses to standard chemotherapy. These results also indicate that E1B-55K might be a novel agent for enhancing treatment responses for cisplatin-resistant ovarian cancer.
- Platinum sensitivity of ovarian cancer cells does not influence their ability to induce M2-type macrophage polarization. [Journal Article]
- AJAm J Reprod Immunol 2018 Jun 14; :e12996
- CONCLUSIONS: Our results provide the evidence for bidirectional interplay between cancer cells and macrophages. Independent of platinum resistance status, ovarian cancer cells polarize macrophages toward M2-like type, whereas macrophages induce epithelial-mesenchymal transition and stemness-related gene expression profile in cisplatin-sensitive, but not cisplatin-resistant cancer cells.
- The lncRNA TP73-AS1 promotes ovarian cancer cell proliferation and metastasis via modulation of MMP2 and MMP9. [Journal Article]
- JCJ Cell Biochem 2018 Jun 15
- Ovarian cancer is one of the most common gynecologic malignancy with poor prognosis. Recently, long noncoding RNAs (lncRNAs) have been identified as key regulators in cancer development. The current ...
Ovarian cancer is one of the most common gynecologic malignancy with poor prognosis. Recently, long noncoding RNAs (lncRNAs) have been identified as key regulators in cancer development. The current study investigated the role of lncRNA P73 antisense RNA 1T (TP73-AS1) in ovarian cancer. Quantitative real-time polymerase chain reaction determined the expression levels of TP-73AS1, matrix metallopeptidases (MMPs) messenger RNA. Cell proliferative ability, cell invasion, and migration were CCK-8 and colony formation, and transwell invasion and migration assays, respectively. The protein levels of matrix metallopeptidase 2 (MMP2) and MMP9 were measured by Western blot. TP73-AS1 was upregulated in the ovarian cancer tissues and ovarian cancer cells, and upregulation of TP73-AS1 was associated with poor prognosis. Knockdown of TP73-AS1 significantly suppressed cell proliferation, invasion, and migration of SKOV3 cells, and overexpression of TP73-AS1 promoted cell proliferation, invasion, and migration of OVCA429 cells. In addition, knockdown of TP73-AS1 suppressed the in vivo tumor growth. Tumor metastasis RT2 profiler polymerase chain reaction array showed that MMP2 and MMP9 was significantly upregulated by TP73-AS1 overexpression in ovarian cancer cells. TP73-AS1 overexpression enhanced the expression of MMP2 and MMP9 in ovarian cancer cells. Knockdown of MMP2 and MMP9 attenuated the effects of TP73-AS1 overexpression on cell invasion and migration. The clinical data showed that MMP2 and MMP9 were upregulated and positively correlated with TP73-AS1 expression in ovarian cancer tissues. Collectively, our results demonstrated the oncogenic role of TP73-AS1 in ovarian cancer, and targeting TP73-AS1 may represent a novel approach in battling against ovarian cancer.
- TPX2 gene silencing inhibits cell proliferation and promotes apoptosis through negative regulation of AKT signaling pathway in ovarian cancer. [Journal Article]
- JCJ Cell Biochem 2018 Jun 15
- Ovarian cancer (OC) is the leading cause of death from gynecological malignancy. Accumulated studies have revealed that targeting protein for Xklp2 (TPX2) was tightly associated with the development ...
Ovarian cancer (OC) is the leading cause of death from gynecological malignancy. Accumulated studies have revealed that targeting protein for Xklp2 (TPX2) was tightly associated with the development and progression of OC. The present study further determined a novel mechanism of TPX2 in OC via the AKT signaling pathway. The differentially expressed genes were screened in GEO database for gene expression microarray of OC. Bioinformatics was used to analyze the key differentially expressed genes in OC. We prepared CD133/1+ OC stem cells. Then cells were treated with TPX2-1 siRNA and perifcsine to explore the correlation of TPX2 and the AKT signaling pathway. We determined the expression of TPX2, AKT, Pl3 K, PTEN, caspase-3, Bax and Bcl-2 in OC cells. Cell proliferation, migration, invasion, and apoptosis rate were respectively measured using MTT and EdU assays, Transwell assay, Scratch test, and flow cytometry. Xenograft tumor in nude mice was used to determine the effect of TPX2 in OC cells in vitro. Initially, TPX2 overexpression was observed in OC, and TPX2 mediated the effect of the AKT signaling pathway in OC. TPX2 knockdown decreased expression of AKT, Pl3 K, and Bcl-2, and the extent of AKT phosphorylation, but increased expression of PTEN, Caspase-3, and Bax. Furthermore, TPX2 knockdown suppressed OC cell proliferation, migration and invasion, but promoted OC cell apoptosis. Taken together, TPX2 silencing negatively regulates the AKT signaling pathway by which OC cell proliferation was inhibited yet cell apoptosis was accelerated, suggesting a potential therapeutic approach to OC.
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- Fibroblast growth factor 18 promotes the growth, migration and invasion of MDA‑MB‑231 cells. [Journal Article]
- OROncol Rep 2018 Jun 07
- Fibroblast growth factor 18 (FGF18) increases cell motility and invasion in colon tumors, and is linked with ovarian and lung tumors. Furthermore, the increased expression of FGF18 mRNA and protein h...
Fibroblast growth factor 18 (FGF18) increases cell motility and invasion in colon tumors, and is linked with ovarian and lung tumors. Furthermore, the increased expression of FGF18 mRNA and protein has been associated with poor overall survival in cancer patients. However, its function has not been investigated in breast cancer. In the present study, we demonstrated that FGF18 promoted cell growth and metastasis in vitro and stimulated tumor growth in xenograft models in vivo. FGF18 mediated the proliferation of MDA‑MB‑231 cells via the ERK/c‑Myc signaling pathway and induced epithelial‑to‑mesenchymal transition (EMT) factors to promote cancer migration and invasion. The decreased expression of FGF18 was strongly correlated with the loss/reduction of p‑ERK, c‑Myc, N‑cadherin, vimentin and Snail 1 protein in MDA‑MB‑231 cells. Collectively, our results indicated that FGF18 played an important role in the growth and metastasis of breast cancer via the ERK/c‑Myc signaling pathway and EMT, indicating that FGF18 may be a potential molecular treatment target for breast cancer.