NEK5 promotes breast cancer cell proliferation through up‐regulation of Cyclin A2

Pei, Jing; Zhang, Jing; Yang, Xiaowei; Wu, Zhengsheng; Sun, Chenyu; Wang, Zhaorui; Wang, Benzhong

doi:10.1002/mc.22982

Cited by 22 publications

(27 citation statements)

References 17 publications

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“…promotes the cell cycle G1/S and G2/M transitions [48]. In breast cancer, NEK5-dependent CCNA2 overexpression promotes the proliferation of tumour cells [49]. Moreover, CCNA2 had significant predictive value for the prognosis of ER+ breast cancer patients as well as tamoxifen resistance [50].…”

Section: Discussionmentioning

confidence: 99%

Identification of five hub genes as monitoring biomarkers for breast cancer metastasis in silico

et al. 2019

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Background: Breast cancer is one of the most common endocrine cancers among females worldwide. Distant metastasis of breast cancer is causing an increasing number of breast cancer-related deaths. However, the potential mechanisms of metastasis and candidate biomarkers remain to be further explored. Results: The gene expression profiles of GSE102484 were downloaded from the Gene Expression Omnibus (GEO) database. Weighted gene co-expression network analysis (WGCNA) was used to screen for the most potent gene modules associated with the metastatic risk of breast cancer, and a total of 12 modules were identified based on the analysis. In the most significant module (R 2 = 0.68), 21 network hub genes (MM > 0.90) were retained for further analyses. Next, protein-protein interaction (PPI) networks were used to further explore the biomarkers with the most interactions in gene modules. According to the PPI networks, five hub genes (TPX2, KIF2C, CDCA8, BUB1B, and CCNA2) were identified as key genes associated with breast cancer progression. Furthermore, the prognostic value and differential expression of these genes were validated based on data from The Cancer Genome Atlas (TCGA) and Kaplan-Meier (KM) Plotter. Receiver operating characteristic (ROC) curve analysis revealed that the mRNA expression levels of these five hub genes showed excellent diagnostic value for breast cancer and adjacent tissues. Moreover, these five hub genes were significantly associated with worse distant metastasis-free survival (DMFS) in the patient cohort based on KM Plotter. Conclusion: Five hub genes (TPX2, KIF2C, CDCA8, BUB1B, and CCNA2) associated with the risk of distant metastasis were extracted for further research, which might be used as biomarkers to predict distant metastasis of breast cancer.

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Section: Discussionmentioning

confidence: 99%

Identification of five hub genes as monitoring biomarkers for breast cancer metastasis in silico

et al. 2019

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“…Different groups have studied each member of this protein family separately and have observed that the expression of many of them is altered in cancers tissues. The expression of NEK2, NEK6, and NEK11 were related to colorectal cancer [30,[38][39][40], NEK2, NEK3, NEK5, NEK6, and NEK8 to breast cancer [11,[41][42][43][44][45], and NEK2 and NEK6 to prostate cancer [16,46].…”

Section: Discussionmentioning

confidence: 96%

Expression of the NEK family in normal and cancer tissue: an immunohistochemical study

et al. 2020

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Background: The NEK serine/threonine protein kinases are involved in cell cycle checkpoints, DNA damage repair, and apoptosis. Alterations in these pathways are frequently associated with cell malignant cellular transformations. Thyroid cancer is the most common malignant tumour in the endocrine system. Despite good treatment methods, the number of cases has increased significantly in recent years. Here, we studied the expression of NEK1, NEK2, NEK3, and NEK5 in different types of normal and malignant tissues, using tissue microarray analysis, and identified NEKs as potential markers in thyroid malignancy. Methods: The studied cases comprised multiple cancer tissue microarrays, including breast, colon, esophagus, kidney, lung, pancreas, prostate, stomach, thyroid and uterine cervix, as well as 281 patients who underwent thyroid resection for thyroid cancer or thyroid nodules. The expression of NEK1, NEK2, NEK3, and NEK5 was analyzed by immunohistochemistry. The expression pattern was evaluated in terms of intensity by two methods, semiquantitative and quantitative, and was compared between normal and cancer tissue. Results: We analysed the expression of each member of the NEK family in a tissue-dependent manner. Compared to normal tissue, most of the evaluated proteins showed lower expression in lung tumour. However, in the thyroid, the expression was higher in malignant tissue, especially for NEK 1, NEK3 and NEK5. Concerning characteristics of the thyroid tumour, such as aggressiveness, NEK1 expression was higher in tumours with multifocality and in patients with lymph node metastasis. NEK3 expression was stronger in patients with stage II, that involved metastasis. NEK5, on the other hand, showed high expression in patients with invasion and metastasis and in patients with tumour size > 4 cm. Furthermore, this work, demonstrated for the first time a high specificity and sensitivity of over-expression of NEK1 in classical and follicular variants of papillary thyroid cancer and NEK3 in tall-cell papillary thyroid cancer. Conclusion: Taken together, the NEK protein kinases emerge as important proteins in thyroid cancer development and may help to identify malignancy and aggressiveness features during diagnosis. Trial registration: This study was retrospectively registered. www.accamargo.org.br/cientistas-pesquisadores/comitede-etica-em-pequisa-cep.

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“…Upregulation of NEK5 expression in breast cancer cells promoted tumor progression and silencing of NEK5 suppressed proliferation and inhibited migration and invasion. This important study demonstrated an integral role for NEK5 in cell proliferation and migration pathways in breast cancer through regulation of Cyclin A2 function [27].…”

Section: Introductionmentioning

confidence: 85%

NEK5 activity regulates the mesenchymal and migratory phenotype in breast cancer cells

Matossian

Elliott

Hoang

et al. 2021

Breast Cancer Res Treat

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Purpose: Breast cancer remains a prominent global disease affecting women worldwide despite the emergence of novel therapeutic regimens. Metastasis is responsible for most cancer-related deaths, and acquisition of a mesenchymal and migratory cancer cell phenotypes contributes to this devastating disease. The utilization of kinase targets in drug discovery have revolutionized the eld of cancer research but despite impressive advancements in kinase-targeting drugs, a large portion of the human kinome remains under-studied in cancer. NEK5, a member of the Never-in-mitosis kinase family, is an example of such an understudied kinase. Here, we characterized the function of NEK5 in breast cancer.Methods: Stably overexpressing NEK5 cell lines (MCF-7) and shRNA knockdown cell lines (MDA-MB-231, TU-BcX-4IC) were utilized. Cell morphology changes were evaluated using immuno uorescence and quanti cation of cytoskeletal components. Cell proliferation was assessed by Ki-67 staining and transwell migration assays tested cell migration capabilities. In vivo experiments with murine models were necessary to demonstrate NEK5 function in breast cancer tumor growth and metastasis.Results: NEK5 activation altered breast cancer cell morphology and promoted cell migration independent of effects on cell proliferation. NEK5 overexpression or knockdown does not alter tumor growth kinetics but promotes or suppresses metastatic potential in a cell type speci c manner, respectively. Conclusion: While NEK5 activity modulated cytoskeletal changes and cell motility, NEK5 activity affected cell seeding capabilities but not metastatic colonization or proliferation in vivo. Here we characterized NEK5 function in breast cancer systems and we implicate NEK5 in regulating speci c steps of metastatic progression.

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NEK5 promotes breast cancer cell proliferation through up‐regulation of Cyclin A2

Cited by 22 publications

References 17 publications

Identification of five hub genes as monitoring biomarkers for breast cancer metastasis in silico

Identification of five hub genes as monitoring biomarkers for breast cancer metastasis in silico

Expression of the NEK family in normal and cancer tissue: an immunohistochemical study

NEK5 activity regulates the mesenchymal and migratory phenotype in breast cancer cells

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