BECN1-knockout impairs tumor growth, migration and invasion by suppressing the cell cycle and partially suppressing the epithelial-mesenchymal transition of human triple-negative breast cancer cells

  • Authors:
    • Cheng-Lin Wu
    • Shi‑Meng Zhang
    • Li Lin
    • Shan-Shan Gao
    • Kai-Fei Fu
    • Xiao-Dan Liu
    • Yan Liu
    • Li-Jun Zhou
    • Ping-Kun Zhou
  • View Affiliations

  • Published online on: July 5, 2018     https://doi.org/10.3892/ijo.2018.4472
  • Pages: 1301-1312
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Abstract

Beclin1 (BECN1), which directly interacts with B‑cell lymphoma 2, serves an important role in autophagy and is involved in the tumorigenesis of various types of cancer. However, the definite role of BECN1 in breast cancer remains controversial. Bi-allelic knockout of Becn1 in a mouse model leads to an embryonic lethal phenotype, which hampers further investigation. To generate cell lines with knockout of BECN1, the CRISPR/Cas9 technique was used to disrupt BECN1 in human triple-negative breast cancer (TNBC) MDA‑MB‑231 cells. To the best of our knowledge, the present study was the first to successfully disrupt BECN1 in MDA‑MB‑231 cells and to screen three stable monoclonal BECN1‑knockout cell lines, suggesting that BECN1‑knockout is not lethal in TNBC cells. Functional analysis revealed that complete loss of BECN1 suppressed MDA‑MB‑231 proliferation and colony formation via inducing G0/G1 cell cycle arrest, not apoptosis, in vitro. On the other hand, BECN1‑knockout inhibited the migratory and invasive ability of MDA‑MB‑231 cells by partially reversing signals of epithelial-mesenchymal transition. Finally, analysis of publicly available gene expression datasets revealed increased expression of BECN1 in TNBC samples. Taken together, the results of the present study identified BECN1 as an oncogene, providing a novel potential target for the treatment of TNBC.
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September-2018
Volume 53 Issue 3

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Wu C, Zhang SM, Lin L, Gao S, Fu K, Liu X, Liu Y, Zhou L and Zhou P: BECN1-knockout impairs tumor growth, migration and invasion by suppressing the cell cycle and partially suppressing the epithelial-mesenchymal transition of human triple-negative breast cancer cells. Int J Oncol 53: 1301-1312, 2018.
APA
Wu, C., Zhang, S., Lin, L., Gao, S., Fu, K., Liu, X. ... Zhou, P. (2018). BECN1-knockout impairs tumor growth, migration and invasion by suppressing the cell cycle and partially suppressing the epithelial-mesenchymal transition of human triple-negative breast cancer cells. International Journal of Oncology, 53, 1301-1312. https://doi.org/10.3892/ijo.2018.4472
MLA
Wu, C., Zhang, S., Lin, L., Gao, S., Fu, K., Liu, X., Liu, Y., Zhou, L., Zhou, P."BECN1-knockout impairs tumor growth, migration and invasion by suppressing the cell cycle and partially suppressing the epithelial-mesenchymal transition of human triple-negative breast cancer cells". International Journal of Oncology 53.3 (2018): 1301-1312.
Chicago
Wu, C., Zhang, S., Lin, L., Gao, S., Fu, K., Liu, X., Liu, Y., Zhou, L., Zhou, P."BECN1-knockout impairs tumor growth, migration and invasion by suppressing the cell cycle and partially suppressing the epithelial-mesenchymal transition of human triple-negative breast cancer cells". International Journal of Oncology 53, no. 3 (2018): 1301-1312. https://doi.org/10.3892/ijo.2018.4472