OncoTargets and Therapy (Apr 2021)

Actin-Like Protein 8 Promotes the Progression of Triple-Negative Breast Cancer via Activating PI3K/AKT/mTOR Pathway

  • Fan S,
  • Yan S,
  • Yang Y,
  • Shang J,
  • Hao M

Journal volume & issue
Vol. Volume 14
pp. 2463 – 2473

Abstract

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Shaoxia Fan,* Shen Yan,* Yang Yang, Jian Shang, Min Hao Breast and Thyroid Surgery, Dongying People’s Hospital, Dongying, Shandong, 257091, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yang YangBreast and Thyroid Surgery, Dongying People’s Hospital, No. 317, Dongying, Shandong, 257091, People’s Republic of ChinaEmail [email protected]: The purpose of this study was to investigate the function of actin-like protein 8 (ACTL8) on triple-negative breast cancer (TNBC) and its potential mechanisms.Methods: In our study, ACTL8 expression and the prognostic values of ACTL8 were evaluated via the dataset from the Cancer Genome Atlas (TCGA). At the same time, the expression of ACTL8 in TNBC cells was measured by Western blot and qRT-PCR. Then, the effects of ACTL8 on the growth and metastasis of TNBC were investigated by using 5-ethynyl-20-deoxyuridine (EdU), colony formation, flow cytometry, wound healing and transwell assays. Mechanistically, Western blot was performed to confirm the interaction between ACTL8 and phosphatidylinositol 3′-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathway in TNBC.Results: ACTL8 expression was upregulated in TNBC and associated with the poor prognosis of TNBC. Silencing ACTL8 suppressed the proliferation, migration and invasion, also promoted the apoptosis in MDA-MB-231 and BT-549 cells. Moreover, we found that silencing ACTL8 could inhibit the activation of PI3K/AKT/mTOR signaling pathway in MDA-MB-231 and BT-549 cells. Meanwhile, the impact of silencing ACTL8 on the proliferation, apoptosis, migration and invasion was enhanced by PI3K/AKT/mTOR pathway inhibitor (Wortmannin) and reversed by PI3K/AKT/mTOR pathway activator (740Y-P).Conclusion: Our data demonstrated that ACTL8 may facilitate the proliferation, migration and invasion, while inhibiting apoptosis through activating PI3K/Akt/mTOR signaling pathway in TNBC.Keywords: TNBC, ACTL8, proliferation, migration, invasion, PI3K/AKT/mTOR pathway

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