Overexpression of α2 subunit of Na-K-ATPase suppresses invasion and migration of human breast cancer cells <italic style="font-style: italic">in vitro</italic> by inhibiting the Src/PI3K/Akt signaling pathway

Yi QIN; Hongfan YUAN; Beilei ZENG; Fang ZHANG; Tingxiu XIANG; Guosheng REN

doi:10.16016/j.1000-5404.201906041

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Overexpression of α2 subunit of Na-K-ATPase suppresses invasion and migration of human breast cancer cells in vitro by inhibiting the Src/PI3K/Akt signaling pathway

Basic Medicine | 更新时间：2026-01-09

- Overexpression of α2 subunit of Na-K-ATPase suppresses invasion and migration of human breast cancer cells in vitro by inhibiting the Src/PI3K/Akt signaling pathway
- Journal of Third Military Medical University Vol. 41, Issue 22, Pages: 2166-2173(2019)
- 作者机构：
  
  1.400016 重庆，重庆医科大学分子肿瘤与表观遗传学重庆市重点实验室
  2.400016 重庆，重庆医科大学附属第一医院:内分泌乳腺外科
  3.400016 重庆，重庆医科大学附属第一医院:消化内科
- 作者简介：
- 基金信息：
  
  the International Cooperation and Exchange Program of National Natural Science Foundation of China(31420103915)
- DOI：10.16016/j.1000-5404.201906041
  CLC： R345; R730.23; R737.9
- Received：19 June 2019，
  
  Revised：2019-08-20，
  
  Published：30 November 2019
- 稿件说明：
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Yi QIN, Hongfan YUAN, Beilei ZENG, et al. Overexpression of α2 subunit of Na-K-ATPase suppresses invasion and migration of human breast cancer cells in vitro by inhibiting the Src/PI3K/Akt signaling pathway[J]. Journal of Third Military Medical University, 2019, 41(22): 2166-2173.
DOI：

Yi QIN, Hongfan YUAN, Beilei ZENG, et al. Overexpression of α2 subunit of Na-K-ATPase suppresses invasion and migration of human breast cancer cells in vitro by inhibiting the Src/PI3K/Akt signaling pathway[J]. Journal of Third Military Medical University, 2019, 41(22): 2166-2173. DOI： 10.16016/j.1000-5404.201906041.

摘要

目的

探讨ATP1A2在人乳腺癌组织与细胞中的表达水平及其对乳腺癌细胞侵袭和迁移能力的影响。

方法

分析the Cancer Genome Atlas (TCGA)数据库中ATP1A2在正常乳腺组织和乳腺癌组织中的表达差异，以及在有无远处转移的患者组织中的表达情况；对过表达ATP1A2的MDA-MB-231和SK-BR-3细胞进行细胞划痕实验、Transwell侵袭和迁移实验，以研究其对乳腺癌细胞侵袭和迁移能力的影响；通过Western blot检测Src、PI3K、Akt蛋白的激活情况。

结果

ATP1A2在乳腺癌组织中的表达低于正常乳腺组织(

0.05)；远处转移的患者组织中ATP1A2的表达低于无远处转移的患者组织(

0.05)；划痕实验和Transwell侵袭、迁移实验中，ATP1A2过表达组的划痕愈合能力及侵袭和迁移出小室的细胞数均少于对照组(

0.05)；Western blot实验发现:过表达组的Src、PI3K、Akt蛋白的磷酸化水平受到抑制(

0.05)。

结论

ATP1A2在人乳腺癌组织中低表达，其表达可能与乳腺癌患者的远处转移相关；过表达ATP1A2后能显著抑制乳腺癌细胞的侵袭和迁移能力，此种作用可能是通过抑制Src/PI3K/Akt信号通路而产生的。

Abstract

Objective

To investigate the expression of α2 subunit of Na-K-ATPase (ATP1A2) in human breast cancer and the effects of ATP1A2 overexpression on the invasion and migration of breast cancer cells

in vitro

Methods

Based on the data from the Cancer Genome Atlas (TCGA) database

the differences of ATP1A2 expression were analyzed between normal breast tissue and breast cancer tissue and between breast cancer patients with and without distal metastasis. The breast cancer MDA-MB-231 and SK-BR-3 cells transfected with pEZ-M35-ATP1A2 plasmid for ATP1A2 overexpression were evaluated for invasion and migration abilities using wound healing test and Transwell invasion and migration tests; The activation of Src

PI3K and Akt proteins in the transfected cells was detected with Western blotting.

Results

The expression of ATP1A2 was significantly lower in breast cancer tissues than in normal breast tissues

and was also lower in patients with than in those without distal metastasis. In wound healing test and Transwell invasion and migration tests

the breast cancer cells with ATP1A2 overexpression showed significantly lowered invasion and migration abilities as compared with the control cells. Western blotting showed that ATP1A2 overexpression significantly reduced the phosphorylation levels of Src

PI3K and Akt proteins in the breast cancer cells.

Conclusion

ATP1A2 is lowly expressed in human breast cancer tissues and shows a likely correlation with distal metastasis. Overexpression of ATP1A2 can significantly inhibit the invasion and migration of breast cancer cells in vitro possibly by inhibiting the Src/PI3K/Akt signaling pathway.

关键词

Keywords

references

LINGREL J B. The physiological significance of the cardiotonic steroid/ouabain-binding site of the Na, K-ATPase[J]. Annu Rev Physiol, 2010, 72(1): 395-412. DOI: 10.1146/annurev-physiol-021909-135725.

XIE Z. Na + -K + -ATPase-mediated signal transduction: from protein interaction to cellular function[J ] . Mol Interv, 2003, 3(3): 157-168. DOI: 10.1124/mi.3.3.157..

NEWMAN R A, YANG P, PAWLUS A D, et al . Cardiac glycosides as novel cancer therapeutic agents[J ] . Mol Interv, 2008, 8(1): 36-49. DOI: 10.1124/mi.8.1.8.

MENGER L, VACCHELLI E, ADJEMIAN S, et al . Cardiac glycosides exert anticancer effects by inducing immunogenic cell death[J ] . Sci Transl Med, 2012, 4(143): 143ra99.DOI: 10.1126/scitranslmed.3003807.

BAGROV A Y, SHAPIRO J I, FEDOROVA O V. Endogenous cardiotonic steroids: physiology, pharmacology, and novel therapeutic targets[J]. Pharmacol Rev, 2009, 61(1): 9-38. DOI: 10.1124/pr.108.000711.

SWEADNER K J. Isozymes of the Na + /K + -ATPase[J ] . Biochim Et Biophys Acta, 1989, 988(2): 185-220. DOI: 10.1016/0304-4157(89)90019-1..

LINGREL J B, KUNTZWEILER T. Na + , K + -ATPase[J ] . J Biol Chem, 1994, 269 (31): 19659-19662..

MIJATOVIC T, ROLAND I, VAN QUAQUEBEKE E, et al . The α1 subunit of the sodium pump could represent a novel target to combat non-small cell lung cancers[J ] . J Pathol, 2007, 212(2): 170-179. DOI: 10.1002/path.2172.

BENARROCH E E. Na + , K + -ATPase: Functions in the nervous system and involvement in neurologic disease[J ] . Neurology, 2011, 76(3): 287-293. DOI: 10.1212/wnl.0b013e 3182074c2f..

MIJATOVIC T, DUFRASNE F, KISS R. Na + /K + -ATPase and cancer[J ] . Pharm Pat Anal, 2012, 1(1): 91-106. DOI: 10.4155/ppa.12.3..

MATHIEU V, PIRKER C, MARTIN DE LASSALLE E, et al . The sodium pump alpha1 sub-unit: a disease progression-related target for metastatic melanoma treatment[J ] . J Cell Mol Med, 2009, 13(9B): 3960-3972. DOI: 10.1111/j.1582-4934.2009.00708.x.

XU Z W, WANG F M, GAO M J, et al . Targeting the Na + /K + -ATPase α1 subunit of hepatoma HepG2 cell line to induce apoptosis and cell cycle arresting[J ] . Biol Pharm Bull, 2010, 33(5): 743-751. DOI: 10.1248/bpb.33.743..

HE Y, ZHANG P, ZHANG D, et al . Combined assessment of low PGRMC1/positive ATP1A1 levels has enhanced prognostic value for renal cell carcinoma[J ] . Oncol Rep, 2018, 40(3): 1467-1476. DOI: 10.3892/or.2018.6541.

ZHANG D, ZHANG P, YANG P B, et al . Downregulation of ATP1A1 promotes cancer development in renal cell carcinoma[J ] . Clin Proteom, 2017, 14: 15. DOI: 10.1186/s12014-017-9150-4.

BAKER BECHMANN M, ROTOLI D, MORALES M, et al . Na, K-ATPase isozymes in colorectal cancer and liver metastases[J ] . Front Physiol, 2016, 7: 9. DOI: 10.3389/fphys.2016.00009.

GOJIS O, RUDRARAJU B, GUDI M, et al . The role of SRC-3 in human breast cancer[J ] . Nat Rev Clin Oncol, 2010, 7(2): 83-89. DOI: 10.1038/nrclinonc.2009.219.

KIM L C, SONG L X, HAURA E B. Src kinases as therapeutic targets for cancer[J]. Nat Rev Clin Oncol, 2009, 6(10): 587-595. DOI: 10.1038/nrclinonc.2009.129.

MIJATOVIC T, INGRASSIA L, FACCHINI V, et al . Na + /K + -ATPase α subunits as new targets in anticancer therapy[J ] . Expert Opin Ther Targets, 2008, 12(11): 1403-1417. DOI: 10.1517/14728222.12.11.1403..

XIE J, YE Q, CUI X, et al . Expression of rat Na-K-ATPase α2 enables ion pumping but not ouabain-induced signaling in α1-deficient Porcine renal epithelial cells[J ] . Am J Physiol Cell Physiol, 2015, 309(6): C373-C382. DOI: 10.1152/ajpcell.00103.2015.

STAEHR C, HANGAARD L, BOUZINOVA E V, et al . Smooth muscle Ca 2+ sensitization causes hypercontractility of middle cerebral arteries in mice bearing the familial hemiplegic migraine type 2 associated mutation[J ] . J Cereb Blood Flow Metab, 2019, 39(8): 1570-1587. DOI: 10.1177/0271678x18761712..

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Overexpression of α2 subunit of Na-K-ATPase suppresses invasion and migration of human breast cancer cells in vitro by inhibiting the Src/PI3K/Akt signaling pathway

DOI：10.16016/j.1000-5404.201906041

摘要

Abstract

关键词

Keywords

references