Aurora kinase A induces papillary thyroid cancer lymph node metastasis by promoting cofilin-1 activity

Maimaiti, Yusufu; Tan, Jie; Zhou, Jing; Wang, Changwen; Pan, Yu; Chen, Chen; Huang, Tao

doi:10.1016/j.bbrc.2016.03.081

Cited by 29 publications

(26 citation statements)

References 32 publications

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“…In the present work, we demonstrate that the expression of NEK1 might be used as a predictive factor for lymph node metastasis in patients with DTC (Differentiated thyroid cancer). In a PTC (Papillary thyroid carcinoma) lymph node metastasis mouse model, tissue microarray data showed that simultaneous over-expression of protein kinase Aurora-A and CFL-1 (a regulator of actin polymerization) correlated with lymph node metastasis in thyroid cancer tissue [58].…”

Section: Discussionmentioning

confidence: 99%

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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Section: Discussionmentioning

confidence: 99%

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

et al. 2020

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“…Cofilin is inactivated by phosphorylation at Ser-3 by LIM kinase and reactivated by dephosphorylation by SSH-1L [ 13 ]. This determines the invasive and metastatic phenotype of tumor cells [ 4 , 22 ]; moreover, our previous work demonstrated that cofilin overexpression is associated with thyroid cancer cell migration [ 24 ]. In this study, we examined the role of SSH-1L on breast cancer cell migration and found that SSH-1L was up-regulated in breast cancer cell lines with high metastatic potential.…”

Section: Resultsmentioning

confidence: 99%

Slingshot-1L, a cofilin phosphatase, induces primary breast cancer metastasis

et al. 2017

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Slingshot (SSH) is a member of the conserved family of cofilin phosphatases that plays a critical role in cell membrane protrusion and migration by transforming inactive phosphorylated cofilin to an active form. SSH-like protein 1 (SSH-1L) expression is detected in various types of tumors; insulin induces the phosphatases activity of SSH-1L in a phosphoinositide 3-kinase-dependent manner. However, little is known about the expression and role of SSH-1L in breast cancer. Here, we analyzed 295 human breast cancer tissue specimens for SSH-1L expression by immunohistochemistry. The correlation between SSH-1L level and patients’ clinical characteristics was analyzed with Pearson’s χ2 test. The function of SSH-1L was evaluated by gene knockdown and quantitative real-time polymerase chain reaction detection of cofilin expression in MDA-MB-231, MCF-7, and SK-BR-3 human breast cancer cell lines. SSH-1L expression was detected in 88.1% of tissue specimens by immunohistochemistry and was strongly associated with increased metastasis and mortality. Loss of SSH-1L expression decreased the nonphosphorylated, active form of cofilin in SK-BR-3 and MDA-MB-231 cell lines, which was associated with reduced cell motility. Accordingly, SSH-1L/cofilin signaling played a critical role in primary breast cancer metastasis and was a potential therapeutic target for breast cancer treatment.

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“…Kozyreva et al revealed that the combination of an Aurora A inhibitor with eribulin could lead to a synergistic increase in apoptosis in mammary tumours, as well as cytotoxic autophagy in metastases (24). Maimaiti et al reported that the simultaneous overexpression of Aurora A and CFL-1 associated with lymph node metastasis in thyroid cancer (25). The inhibition of Aurora A suppressed thyroid cancer cell migration in vitro and decreased lymph node metastasis in nude mice (25).…”

Section: Discussionmentioning

confidence: 99%

“…Maimaiti et al reported that the simultaneous overexpression of Aurora A and CFL-1 associated with lymph node metastasis in thyroid cancer (25). The inhibition of Aurora A suppressed thyroid cancer cell migration in vitro and decreased lymph node metastasis in nude mice (25). Notably, the roles of Aurora A overexpression in drug-resistance in tumour cells remain unclear.…”

Section: Discussionmentioning

confidence: 99%

miRNA‑885‑3p inhibits docetaxel chemoresistance in lung adenocarcinoma by downregulating Aurora�A

et al. 2018

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Aurora A is a member of the mitotic serine/threonine kinase family. It is involved in key processes during mitosis and meiosis, and Aurora A upregulation is implicated in malignant transformation. In the present study, we revealed that Aurora A expression was significantly higher in docetaxel-resistant lung adenocarcinoma (LAD) cells than in parental cells. Higher levels of Aurora A expression were significantly correlated with higher chemoresistance and proliferation in LAD cells, while silencing Aurora A promoted caspase-3-dependent cell apoptosis by downregulating NF-κB and Bcl-2 and upregulating Bax expression. In addition, an increased proportion of cells in the G2/M phase and a decreased proportion of cells in the S phase were observed due to the suppression of Aurora A. Furthermore, we identified that microRNA-885-3p (miR-885-3p) could target Aurora A directly. There was significantly lower miR-885-3p expression in docetaxel-resistant LAD cells than in parental LAD cells. miR-885-3p could modulate the docetaxel response, cell proliferation and apoptosis in LAD cells in vitro. Moreover, we found that Aurora A overexpression or miR-885-3p inhibition was associated with more aggressive behaviour in LAD cells. Thus, miR-885-3p/Aurora A may be involved in the chemoresistance of LAD cells, and assessing miR-885-3p/Aurora A expression may be a potential method for indicating chemosensitivity to docetaxel-based chemotherapy.

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Aurora kinase A induces papillary thyroid cancer lymph node metastasis by promoting cofilin-1 activity

Cited by 29 publications

References 32 publications

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

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

Slingshot-1L, a cofilin phosphatase, induces primary breast cancer metastasis

miRNA‑885‑3p inhibits docetaxel chemoresistance in lung adenocarcinoma by downregulating Aurora�A

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