Knockdown CD44 Promotes Amyloid-Beta Degradation in Ovarian Cancer Cells By Regulating CD36 Expression

Abstract Background: CD44 is highly expressed in many cancers, including ovarian cancer. Its interactions with ligands are involved in tumor progression, prognosis, and metastasis. However, the function of CD44 in the advancement of ovarian cancer remains unclear. Methods and Results: RNA sequencing was used to investigate the possible molecules and pathways regulated by CD44 in ovarian cancer to compare gene expression in CD44-knockdown SKOV3 cells and control cells. Identify the differentially expressed genes and then proceed to functional enrichment analysis. The results showed that genes differentially expressed were enriched in ECM-receptor interaction, Protein digestion and absorption, Focal adhesion, Notch signaling pathway, microRNA in cancer, and TGF-beta signaling pathway. Furthermore, the analysis of the proteins interaction network revealed the interaction between CD44 and CD36 in SKOV3 cells. Further analysis showed that CD36, a molecule that may be involved in ECM-receptor interaction, was low expressed in CD44-knockdown SKOV3 cells. And the results showed that knockdown CD44 induces amyloid-beta degradation in ovarian cancer cells by regulating CD36 expression. The analyses of the public database demonstrated that the CD36 expression was related to the clinical survival of ovarian cancer. Conclusions: Our study showed that CD44 might up-regulate the CD36 expression in ovarian cancer, thereby exerting a cancer-promoting effect.

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UBE2S promotes the progression and Olaparib resistance of ovarian cancer through Wnt/β-catenin signaling pathway

Journal of Ovarian Research ◽

10.1186/s13048-021-00877-y ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Wenjing Hu ◽

Min Li ◽

Youguo Chen ◽

Xinxian Gu

Keyword(s):

Ovarian Cancer ◽

Cancer Cells ◽

Signaling Pathway ◽

Xenograft Model ◽

Migration And Invasion ◽

Ovarian Cancer Cells ◽

Dependent Manner ◽

Cancer Proliferation ◽

Skov3 Cells

Abstract Background Ovarian cancer is the most lethal gynecologic malignancy worldwide. Olaparib, an inhibitor of poly (ADP-ribose) polymerase (PARP), is becoming widely used in ovarian cancer treatment. The overall survival of ovarian cancer has not been significantly changed over the past decades and ovarian cancer has become increasingly resistant to the Olaparib. Ubiquitin-conjugating enzyme E2S (UBE2S) has been proved to promote malignant behaviors in many cancers. However, the function of UBE2S in the development and Olaparib resistance of ovarian cancer are unclear. Materials and methods In this study, we detected the expression of UBE2S in normal fallopian tube (FT) and HGSOC tissues. A2780 and SKOV3 cells were stably transfected with PCMV-UBE2S, PCMV-UBE2S-C95S, UBE2S shRNAs, and negative controls. The CCK8 assay and clonogenic assay were conducted to analyze ovarian cancer proliferation and Olaparib resistance. The transwell assay was performed to determine the migration and invasion of ovarian cancer cells. The relative protein levels of the Wnt/β-catenin signaling pathway were tested using western blot. The ovarian cancer cells were treated with XAV-939 to investigate the role of Wnt/β-catenin signaling pathway in Olaparib resistance. Moreover, we repeated some above procedures in the xenograft model. Results The results demonstrated that UBE2S was highly upregulated in HGSOC and that high UBE2S expression was correlated with poor outcomes in HGSOC. UBE2S promoted ovarian cancer proliferation and drived the migration and invasion of ovarian cancer cells. UBE2S activated the Wnt/β-catenin signaling pathway in ovarian cancer resulting in Olaparib resistance in vitro and in vivo. Furthermore, UBE2S enhanced the proliferation and Olaparib resistance of ovarian cancer in its enzymatic activity dependent manner. Conclusions These data suggest a possible molecular mechanism of proliferation and metastasis of ovarian cancer and highlight the potential role of UBE2S as a therapeutic target in ovarian cancer.

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Apoptotic SKOV3 cells stimulate M0 macrophages to differentiate into M2 macrophages and promote the�proliferation and migration of ovarian cancer�cells by activating the ERK signaling pathway

International Journal of Molecular Medicine ◽

10.3892/ijmm.2019.4408 ◽

2019 ◽

Cited By ~ 1

Author(s):

Qun Zhang ◽

Hui Li ◽

Yiqing Mao ◽

Xi Wang ◽

Xuehui Zhang ◽

...

Keyword(s):

Ovarian Cancer ◽

Cancer Cells ◽

Signaling Pathway ◽

Erk Signaling ◽

Ovarian Cancer Cells ◽

M2 Macrophages ◽

Skov3 Cells ◽

And Migration ◽

Proliferation And Migration

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Propofol inhibits proliferation, migration, invasion and promotes apoptosis by regulating HOST2/JAK2/STAT3 signaling pathway in ovarian cancer cells

Cytotechnology ◽

10.1007/s10616-021-00462-7 ◽

2021 ◽

Vol 73 (2) ◽

pp. 243-252

Author(s):

Xiang Shen ◽

Diaolan Wang ◽

Xu Chen ◽

Jun Peng

Keyword(s):

Ovarian Cancer ◽

Cancer Cells ◽

Signaling Pathway ◽

Ovarian Cancer Cells ◽

Stat3 Signaling ◽

Stat3 Signaling Pathway

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CNOT7 modulates biological functions of ovarian cancer cells via AKT signaling pathway

Life Sciences ◽

10.1016/j.lfs.2020.118996 ◽

2021 ◽

Vol 268 ◽

pp. 118996

Author(s):

Jiangtao Yu ◽

Xiaoli Hu ◽

Xiuxiu Chen ◽

Qiangyong Zhou ◽

Qi Jiang ◽

...

Keyword(s):

Ovarian Cancer ◽

Cancer Cells ◽

Signaling Pathway ◽

Akt Signaling ◽

Ovarian Cancer Cells ◽

Biological Functions ◽

Akt Signaling Pathway

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Dasatinib (BMS-35482) Interacts Synergistically With Docetaxel, Gemcitabine, Topotecan, and Doxorubicin in Ovarian Cancer Cells With High SRC Pathway Activation and Protein Expression

International Journal of Gynecological Cancer ◽

10.1097/igc.0000000000000056 ◽

2014 ◽

Vol 24 (2) ◽

pp. 218-225 ◽

Cited By ~ 5

Author(s):

Angeles Alvarez Secord ◽

Deanna Teoh ◽

Jingquan Jia ◽

Andrew B. Nixon ◽

Lisa Grace ◽

...

Keyword(s):

Ovarian Cancer ◽

Protein Expression ◽

Cancer Cells ◽

Combination Index ◽

Chemotherapeutic Agents ◽

Cytotoxic Agents ◽

Ovarian Cancer Cells ◽

Response Curves ◽

Pathway Activation ◽

Skov3 Cells

PurposeThis study aimed to explore the activity of dasatinib in combination with docetaxel, gemcitabine, topotecan, and doxorubicin in ovarian cancer cells.MethodsCells with previously determined SRC pathway and protein expression (SRC pathway/SRC protein IGROV1, both high; SKOV3, both low) were treated with dasatinib in combination with the cytotoxic agents. SRC and paxillin protein expression were determined pretreatment and posttreatment. Dose-response curves were constructed, and the combination index (CI) for drug interaction was calculated.ResultsIn the IGROV1 cells, dasatinib alone reduced phospho-SRC/total SRC 71% and p-paxillin/t-paxillin ratios 77%. Phospho-SRC (3%–33%; P = 0.002 to 0.04) and p-paxicillin (6%–19%; P = 0.01 to 0.05) levels were significantly reduced with dasatinib in combination with each cytotoxic agent. The combination of dasatinib and docetaxel, gemcitabine, or topotecan had a synergistic antiproliferative effect (CI, 0.49–0.68), whereas dasatinib combined with doxorubicin had an additive effect (CI, 1.08).In SKOV3 cells, dasatinib resulted in less pronounced reductions of phospho-SRC/total SRC (49%) and p-paxillin/t-paxillin (62%). Phospho-SRC (18%; P < 0.001) and p-paxillin levels (18%; P = 0.001; 9%; P = 0.007) were significantly decreased when dasatinib was combined with docetaxel and topotecan (p-paxillin only). Furthermore, dasatinib combined with the cytotoxics in the SKOV3 cells produced an antagonistic interaction on the proliferation of these cells (CI, 1.49–2.27).ConclusionsDasatinib in combination with relapse chemotherapeutic agents seems to interact in a synergistic or additive manner in cells with high SRC pathway activation and protein expression. Further evaluation of dasatinib in combination with chemotherapy in ovarian cancer animal models and exploration of the use of biomarkers to direct therapy are warranted.

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