RRM2 elicits the metastatic potential of breast cancer cells by regulating cell invasion, migration and VEGF expression via the PI3K/AKT signaling

Zhuang,Sujing; Li,Li; Zang,Yuwei; Li,Guangfeng; Wang,Feng

doi:10.3892/ol.2020.11428

RRM2 elicits the metastatic potential of breast cancer cells by regulating cell invasion, migration and VEGF expression via the PI3K/AKT signaling

Authors:
- Sujing Zhuang
- Li Li
- Yuwei Zang
- Guangfeng Li
- Feng Wang
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Affiliations: Department of Neurology, Linyi Central Hospital, Linyi, Shandong 276499, P.R. China, Department of Radiology, Yishui People's Hospital, Linyi, Shandong 276499, P.R. China, Department of Breast Disease, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, P.R. China
Published online on: March 3, 2020 https://doi.org/10.3892/ol.2020.11428
Pages: 3349-3355

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Abstract

Breast cancer is the second leading primary cause for cancer‑related mortality among women and metastasis to the brain is a disastrous event for patients with increasing incidence. A previous study confirmed the critical function of RRM2 in breast cancer cell growth. Unfortunately, the role and fundamental molecular mechanism of RRM2 in breast cancer metastasis remains elusive. In the current study, higher RRM2 expression was validated in breast cancer tissues, especially in the brain metastasis group. Simultaneously, the expression of RRM2 was increased in breast cancer cells relative to the normal breast epithelial cell line MCF‑10A, concomitant with higher levels of RRM2 in the highly metastatic MDA‑MB‑231 cell line relative to the weakly metastatic MCF‑7 cell line. Knockdown of RRM2 by small interfering‑RRM2 transfection notably suppressed the malignant metastatic behavior of breast cancer cells, including invasion and migration. Simultaneously, RRM2 downregulation also restrained the transcription and release of vascular endothelial growth factor (VEGF) in breast cancer cells. Moreover, inhibition of RRM2 dampened the activation of phosphatidylinositol 3 kinase (PI3K)/protein kinase B (AKT) signaling by decreasing phosphorylated‑AKT and downstream matrix metalloproteinases‑2 expression. Intriguingly, reactivation of the PI3K/AKT pathway with its agonist insulin‑like growth factor‑1 reversed the adverse effects of RRM2 suppression on cancer cell invasion, migration and VEGF expression. Together, these findings suggest that RRM2 may act as a pro‑metastatic factor to facilitate breast cancer metastasis by evoking cell invasion, migration and VEGF expression through the PI3K/AKT signaling pathway. This study may provide an attractive target for metastatic intervention in breast cancer.

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