Oncotarget

Research Papers:

The requirement of SEPT2 and SEPT7 for migration and invasion in human breast cancer via MEK/ERK activation

Nianzhu Zhang, Lu Liu, Ning Fan, Qian Zhang, Weijie Wang, Mingnan Zheng, Lingfei Ma, Yan Li and Lei Shi _

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Oncotarget. 2016; 7:61587-61600. https://doi.org/10.18632/oncotarget.11402

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Abstract

Nianzhu Zhang1,*, Lu Liu2,*, Ning Fan2, Qian Zhang1, Weijie Wang1, Mingnan Zheng3, Lingfei Ma4, Yan Li2, Lei Shi1,5

1Institute of Cancer Stem Cell, Cancer Center, Dalian Medical University, Dalian, 116044, Liaoning, P.R.China

2College of Basic Medical Sciences, Dalian Medical University, Dalian, 116044 Liaoning, P.R.China

3Department of Gynecology and Obstetrics, Dalian Municipal Central Hospital Affiliated to Dalian Medical University, Dalian, 116033, Liaoning, P.R.China

4The First Affiliated Hospital of Dalian Medical University, Dalian, 116011, Liaoning, P.R.China

5State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, P.R.China

*These authors contributed equally to this work

Correspondence to:

Lei Shi, email: [email protected]

Yan Li, email: [email protected]

Lingfei Ma, email: [email protected]

Keywords: septin, forchlorfenuron, breast cancer, invasion, MAPK

Received: April 24, 2016     Accepted: July 28, 2016     Published: August 19, 2016

ABSTRACT

Septins are a novel class of GTP-binding cytoskeletal proteins evolutionarily conserved from yeast to mammals and have now been found to play a contributing role in a broad range of tumor types. However, their functional importance in breast cancer remains largely unclear. Here, we demonstrated that pharmaceutical inhibition of global septin dynamics would greatly suppress proliferation, migration and invasiveness in breast cancer cell lines. We then examined the expression and subcellular distribution of the selected septins SEPT2 and SEPT7 in breast cancer cells, revealing a rather variable localization of the two proteins with cell cycle progression. To determine the role of both septins in mediating malignant behavior of cancer cells, we used RNA silencing to specifically deplete endogenous SEPT2 or SEPT7 in highly invasive breast cancer cell line MDA-MB-231. Our findings showed that SEPT2/7 depletion had virtually identical inhibitory effects on cellular proliferation, apoptosis, migration and invasion. Moreover, the opposite performance in migration and invasion was observed after enforced expression of SEPT2/7 in the same cell line. We further demonstrated MEK/ERK activation, but not other MAPKs and AKT, was positively correlated with the protein levels of SEPT2 and SEPT7. Additionally, in SEPT2/7-overexpressing cells, the MEK specific inhibitor U0126 was able to correct the high active status of MEK/ERK while normalizing the increased invasive behaviors of these cells. Taken together, these results strongly suggest that SEPT2 and SEPT7 are involved in breast carcinogenesis and may serve as valuable therapeutic targets for breast cancer.


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