Cisplatin‐resistant cancer cells are sensitive to Aurora kinase A inhibition by alisertib

Wang, Lihong; Arras, Janet; Katsha, Ahmed; Hamdan, Saif; Belkhiri, Abbes; Ecsedy, Jeffrey; El–Rifai, Wael

doi:10.1002/1878-0261.12066

Cited by 30 publications

(32 citation statements)

References 48 publications

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“…It has been reported that ubiquitin ligase FBXO22 [21] mediates the multiubiquitination and degradation of CD147 by interacting with the intracellular domain CD147-ICD of transmembrane glycoprotein CD147, thus reversing the cisplatin resistance of SMMC-7721, Huh-7 and A549 cancer cells. AURKA [22] is activated in gastric cancer and it has been demonstrated that AURKA promotes cisplatin resistance in gastric cancer by regulating eIF4E, c-MYC, HDM2. In this study, we selected the proteins that were not reported related to cisplatin resistance in literature for further study, including CDC20, CHAF1B, PPP1R13L, TRIP12.…”

Section: Discussionmentioning

confidence: 99%

Ubiquitin ligase CHAF1B induces cisplatin resistance in lung adenocarcinoma by promoting NCOR2 degradation

Gong

et al. 2020

Cancer Cell Int

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Background: Lung cancer is the most common malignant tumor in the world. The Whole-proteome microarray showed that ubiquitin ligase chromatin assembly factor 1 subunit B (CHAF1B) expression in A549/DDP cells is higher than in A549 cells. Our study explored the molecular mechanism of CHAF1B affecting cisplatin resistance in lung adenocarcinoma (LUAD). Methods: Proteome microarray quantify the differentially expressed proteins between LUAD cell line A549 and its cisplatin-resistant strain A549/DDP. Quantitative real-time quantitative polymerase chain reaction (qRT-PCR) and Western blot (WB) confirmed the CHAF1B expression. Public databases analyzed the prognosis of LUAD patients with varied LUAD expression followed by the substrates prediction of CHAF1B. Public databases showed that nuclear receptor corepressor 2 (NCOR2) may be substrates of CHAF1B. WB detected that CHAF1B expression affected the expression of NCOR2. Cell and animal experiments and clinical data detected function and integrating mechanism of CHAF1B compounds. Results: Proteome chips results indicated that CHAF1B, PPP1R13L, and CDC20 was higher than A549 in A549/DDP. Public databases showed that high expression of CHAF1B, PPP1R13L, and CDC20 was negatively correlated with prognosis in LUAD patients. PCR and WB results indicated higher CHAF1B expression in A549/DDP cells than that in A549 cells. NCOR2 and PPP5C were confirmed to be substrates of CHAF1B. CHAF1B knockdown significantly increased the sensitivity of cisplatin in A549/DDP cells and the upregulated NCOR2 expression. CHAF1B and NCOR2 are interacting proteins and the position of interaction between CHAF1B and NCOR2 was mainly in the nucleus. CHAF1B promotes ubiquitination degradation of NCOR2. Cells and animal experiments showed that under the action of cisplatin, after knockdown of CHAF1B and NCOR2 in A549/DDP group compared with CHAF1B knockdown alone, the cell proliferation and migratory ability increased and apoptotic rate decreased, and the growth rate and size of transplanted tumor increased significantly. Immunohistochemistry suggested that Ki-67 increased, while apoptosis-related indicators caspase-3 decreased significantly. Clinical data showed that patients with high expression of CHAF1B are more susceptible to cisplatin resistance.

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Section: Discussionmentioning

confidence: 99%

Ubiquitin ligase CHAF1B induces cisplatin resistance in lung adenocarcinoma by promoting NCOR2 degradation

Gong

et al. 2020

Cancer Cell Int

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“…Previous studies demonstrated that AURKA was involved in the susceptibility to hepatitis B virus-related HCC and the progression of head and neck and gastric cancer. High expression of AURKA promoted cisplatin resistance by activating p-eIF4E, c-MYC and HDM2 ( 42 , 43 ). AURKA was found to be amplified in >15–25% of ovarian cancer cell lines and primary tumors ( 40 , 41 ).…”

Section: Discussionmentioning

confidence: 99%

Identifying genes as potential prognostic indicators in patients with serous ovarian cancer resistant to carboplatin using integrated bioinformatics analysis

2018

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Serous ovarian cancer (SOC) accounts for >50% of all epithelial ovarian cancers. However, patients with SOC present with various degrees of response to platinum-based chemotherapy and, thus, their survival may differ. The present study aimed to identify the candidate genes involved in the carcinogenesis and drug resistance of SOC by analyzing the microarray datasets GDS1381 and GDS3592. GDS1381 and GDS3592 were downloaded from the Gene Expression Omnibus database (). A total of 219 differentially expressed genes (DEGs) were identified. Potential genes that may predict the response to carboplatin and, thus, the prognosis of SOC were analyzed. The enriched functions and pathways of DEGs included extracellular region, extracellular space and extracellular exosome, among others. Upon screening the upregulated and downregulated genes on the connectivity map, 10 small-molecule drugs were identified that may be helpful in improving drug sensitivity in patients with ovarian cancer. A total of 30 hub genes were screened for further analysis after constructing the protein-to-protein interaction network. Through survival analysis, comparison of genes across numerous analyses, and immunohistochemistry, GNAI1, non-structural maintenance of chromosomes (non-SMC) condensin I complex subunit H (NCAPH), matrix metallopeptidase 9 (MMP9), aurora kinase A (AURKA) and enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2) were identified as the key molecules that may be involved in the carcinogenesis and carboplatin resistance of SOC. In conclusion, GNAI1, NCAPH, MMP9, AURKA and EZH2 should be examined in further studies for the possibility of their participation in the carcinogenesis and carboplatin response of SOC.

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“…These suggest that EMT pathway might involve in cisplatin resistance. C-myc was also been proven to play an important role in chemoresistance to cisplatin 35 , 36 . Oncoprotein CIP2A could affect EMT pathway and expression of P-Akt by virtue of its control on PP2A and MYC stabilization in many cancer cells 8 , 37 .…”

Section: Discussionmentioning

confidence: 99%

CIP2A Promotes Proliferation, Invasion and Chemoresistance to Cisplatin in Renal Cell Carcinoma

Zhang¹,

Fang²,

Zang³

et al. 2018

J. Cancer

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CIP2A is a well-known oncoprotein whose expression is elevated in multiple human solid tumor types. However, its role in renal cell carcinoma (RCC) development is poorly understood. Thus, in our present study, we used the renal cancer cell lines 786-O, A498 and CAKI-1 and the renal epithelial cell line HK-2 to clarify the function of CIP2A in RCC. We found that CIP2A expression is much higher in the RCC cells than in the normal renal epithelial cell. Lentivirus covered coding region CIP2A cDNA sequence and CIP2A siRNA were used to up and down regulate CIP2A expression in vitro. We found that overexpression of CIP2A promoted G1/S transition and cell proliferation. In addition, up-regulation of CIP2A significantly enhanced the invasion and migration capabilities of the cells. Furthermore, CIP2A promoted epithelial-mesenchymal transformation (EMT) and chemoresistance to cisplatin in RCC cells. Taken together, our findings demonstrate that CIP2A plays an important role in proliferation, invasion and chemoresistance to cisplatin in RCC cells. CIP2A may serve as an ideal molecular target for RCC therapeutics.

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Cisplatin‐resistant cancer cells are sensitive to Aurora kinase A inhibition by alisertib

Cited by 30 publications

References 48 publications

Ubiquitin ligase CHAF1B induces cisplatin resistance in lung adenocarcinoma by promoting NCOR2 degradation

Ubiquitin ligase CHAF1B induces cisplatin resistance in lung adenocarcinoma by promoting NCOR2 degradation

Identifying genes as potential prognostic indicators in patients with serous ovarian cancer resistant to carboplatin using integrated bioinformatics analysis

CIP2A Promotes Proliferation, Invasion and Chemoresistance to Cisplatin in Renal Cell Carcinoma

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