Solute carrier family 6 member 1 promoting the proliferation and invasion of breast cancer cells through affecting the phosphorylation of PI3K/Akt signaling pathway

JI Lei; XU Yang; TANG Nan

doi:10.16098/j.issn.0529-1356.2021.05.013

PDF(11773 KB)

Acta Anatomica Sinica ›› 2021, Vol. 52 ›› Issue (5) : 759-766. DOI: 10.16098/j.issn.0529-1356.2021.05.013

Solute carrier family 6 member 1 promoting the proliferation and invasion of breast cancer cells through affecting the phosphorylation of PI3K/Akt signaling pathway

JI Lei¹ XU Yang¹ TANG Nan^2*

Author information +

History +

Abstract

Objective To investigate the effects of solute carrier family 6 member 1 (SLC6A1) on migration and invasion of breast cancer cells and its molecular mechanism. Methods Data sets GSE125989 and GSE100534 were downloaded and comprehensively analyzed to screen the key genes. Protein interaction network of key genes was constructed by STRING database and Cytoscape 3.6.1 software, and hub genes were screened. Expression of hub gene SLC6A1 in breast cancer and its effect on prognosis were detected by Ualcan datebase and GEPIA datebase. SLC6A1-siRNA plasmid was transfected to interfere with SLC6A1 expression in breast cancer cells. Migration and invasion of breast cancer cells were detected by wound healing assay and Transwell assays. The mechanism of SLC6A1 in breast cancer was detected by gene set enrichment analysis and Western blotting. SC79 was used to activate the Akt pathway, and then detect changes in cell migration and invasion were detected. Results A total of 92 differentially expressed genes between metastatic breast cancer and carcinoma in situ were selected, and 20 hub genes including collagen Ⅰα1(COL1A1),vascular endothelial growth factor A(VEGFA) and SLC6A1 were selected. SLC6A1 were highly expressed in breast cancer tissues (P<0.001) and correlated with prognosis (P=0.01). After SLC6A1 interference, the migration and invasion of breast cancer cells decreased significantly (P<0.05). Inhibition of SLC6A1 expression can inhibit the phosphorylation of PI3K/Akt signaling pathway (P<0.05). Activation of the PI3K/Akt pathway eliminated the inhibitory effect of SLC6A1-siRNA on migration and invasion of breast cancer cells (P<0.05). Conclusion SLC6A1 promotes the migration and invasion of breast cancer cells through the PI3K/Akt signaling pathway.

Key words

Breast cancer / Solute carrier family 6 member 1 / Migration / Invasion / Phosphatidylinositol 3-kinase/protein kinase B / Western blotting / Human

Cite this article

EndNote

Ris (Procite)

Bibtex

Download Citations

JI Lei XU Yang TANG Nan. Solute carrier family 6 member 1 promoting the proliferation and invasion of breast cancer cells through affecting the phosphorylation of PI3K/Akt signaling pathway[J]. Acta Anatomica Sinica. 2021, 52(5): 759-766 https://doi.org/10.16098/j.issn.0529-1356.2021.05.013

References

［1］ Xue ShH, Lu ZhY, Zhang TCh, et al. Expression and mechanism of microRNA-940 in breast cancer ［J］. Acta Anatomica Sinica, 2019, 50(1): 56-62. (in Chinese)
薛世航, 陆振一, 张同成, 等. MicroRNA-940在乳腺癌中的表达变化及作用机制［J］. 解剖学报, 2019, 50(1): 56-62.
［2］ Fan L, Strasserweippl K, Li JJ, et al. Breast cancer in China［J］. Lan Oncol, 2014, 15(7): e279-e289.
［3］ Vogelstein B, Papadopoulos N, Velculescu VE, et al. Cancer genome landscapes ［J］. Science, 2013, 339(6127): 1546-1558.
［4］ Xue D, Cheng P, Han M, et al. An integrated bioinformatical analysis to evaluate the role of KIF4A as a prognostic biomarker for breast cancer［J］. Oncotargets Ther, 2018, 11(1): 4755-4768.
［5］ Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013［J］. CA Cancer J Clin, 2013, 63(1): 11-30.
［6］ Hong W, Dong E. The past, present and future of breast cancer research in China［J］. Cancer Lett, 2014, 351(1): 1-5.
［7］ Gonzalezburgos G. GABA transporter GAT1: a crucial determinant of GABAB receptor activation in cortical circuits ［J］? Adv Pharmacol, 2010, 58: 175-204.
［8］ Kim K, Oh S, Park U, et al. Gene expression profiling using oligonucleotide microarray in atrophic gastritis and intestinal metaplasia［J］. Korean J Gastroenterol, 2007, 49(4): 209-224.
［9］ Maolakuerban N, Azhati B, Tusong H, et al. MiR-200c-3p inhibits cell migration and invasion of clear cell renal cell carcinoma via regulating SLC6A1［J］. Cancer Biol Ther, 2018, 19(4): 282-291.
［10］ Zhao Y, Zhou X, He Y, et al. SLC6A1-miR133a-CDX2 loop regulates SK-OV-3 ovarian cancer cell proliferation, migration and invasion［J］. Oncol Lett, 2018, 16(4): 4977-4983.
［11］ Li ZH, Xiong QY, Xu L, et al. miR-29a regulated ER-positive breast cancer cell growth and invasion and is involved in the insulin signaling pathway［J］. Oncotarget, 2017, 8(20): 32566-32575.
［12］ Gray SG, Mathiasen IS, De Meyts P. The insulin-like growth factors and insulin-signalling systems: an appealing target for breast cancer therapy ［J］? Horm Metab Res, 2003, 35(11-12): 857-871.
［13］ Yang Q, Ji G, Li J. STEAP2 is down-regulated in breast cancer tissue and suppresses PI3K/AKT signaling and breast cancer cell invasion in vitro and in vivo［J］. Cancer Biol Ther, 2020, 21(3): 278-291.
［14］ Sharma VR, Gupta GK, Sharma AK, et al. PI3K/Akt/mTOR intracellular pathway and breast cancer: vactors, mechanism and regulation［J］. Curr Pharm Des, 2016, 23(11): 1633-1638.
［15］ Jung W, Murrell MP, Kim T. F-actin fragmentation induces distinct mechanisms of stress relaxation in the actin cytoskeleton［J］. ACS Macro Lett, 2016, 5(6): 641645.
［16］ Zhao W, Kuai X, Zhou X, et al. Trop2 is a potential biomarker for the promotion of EMT in human breast cancer［J］. Oncol Rep, 2018, 40(2): 759-766.
［17］ Hinz N, Jucker M. Distinct functions of AKT isoforms in breast cancer: a comprehensive review［J］. Cell Com Sig, 2019, 17(1): 1-29.