ACOT7 Promotes the Malignant Biological Behavior of Triple-negative Breast Cancer Cells by Activating the PI3K/AKT Signaling Pathway

Zhijie JIN; Baoting JIAO; Jinxi WANG

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Zhijie JIN, Baoting JIAO, Jinxi WANG. ACOT7 Promotes the Malignant Biological Behavior of Triple-negative Breast Cancer Cells by Activating the PI3K/AKT Signaling Pathway[J]. Journal of Kunming Medical University.

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ACOT7 Promotes the Malignant Biological Behavior of Triple-negative Breast Cancer Cells by Activating the PI3K/AKT Signaling Pathway

1.
Department of Breast Surgery
2.
Department of Thyroid Surgery，Handan First Hospital，Handan Hebei 056000，China

Received Date: 2026-03-17
Available Online: 2026-10-30

Abstract

Abstract

Objective To examine the function of acyl-CoA thioesterase7 （ACOT7） in the malignant biological behavior of triple-negative breast cancer （TNBC） cells and to explore its underlying mechanisms. Methods The expression and prognostic value of ACOT7 in breast cancer were analyzed using the gene expression profiling interactive analysis （GEPIA） database. Western blot was employed to detect the protein expression of ACOT7 in the human normal breast cell line MCF-10A and the triple-negative breast cancer （TNBC） cell lines MDA-MB-468 and MDA-MB-231. ACOT7 knockdown and stable overexpression TNBC cell models were established via si-ACOT7 transfection and lentiviral infection, respectively. CCK-8, plate colony formation, wound healing, and Transwell assays were performed to evaluate the effects of ACOT7 on the malignant biological behaviors of TNBC cells. Western blot was used to examine the effects of ACOT7 on the expression of proteins related to the PI3K/AKT pathway. Immunoprecipitation-mass spectrometry （IP-MS） was applied to screen for ACOT7-interacting proteins in MDA-MB-468 cells, and co-immunoprecipitation （Co-IP） was performed to verify the interaction between ACOT7 and insulin receptor substrate 1 （IRS1） in MDA-MB-468 and MDA-MB-231 cells. Western blot was further conducted to determine the effect of ACOT7 on IRS1 expression. Finally, rescue experiments using the PI3K/AKT pathway agonist IGF-1 and inhibitor LY294002 were carried out to verify whether ACOT7 influences the biological behaviors of TNBC cells by regulating the PI3K/AKT pathway. Results GEPIA database analysis showed that ACOT7 expression was higher in breast cancer tissues than in normal tissues, and patients with high ACOT7 expression had a lower overall survival rate （P < 0.05）. ACOT7 expression was higher in TNBC cells than in MCF-10A cells （P < 0.05）. Functional assays demonstrated that knockdown of ACOT7 inhibited the proliferation, migration, and invasion abilities of TNBC cells and reduced the protein levels of p-PI3K and p-AKT, whereas overexpression of ACOT7 showed the opposite trends （P < 0.05）. IP-MS and Co-IP assays confirmed a protein-protein interaction between ACOT7 and IRS1, and ACOT7 positively regulated IRS1 protein expression （P < 0.05）. Rescue experiment results indicated that IGF-1 partially reversed the inhibitory effects of ACOT7 knockdown on PI3K/AKT signaling pathway activity and the malignant biological behaviors of TNBC cells （P < 0.05）, while LY294002 attenuated the activating effects of ACOT7 overexpression on the above parameters （P < 0.05）. Conclusion ACOT7 may promote the proliferation, migration, and invasion of TNBC cells by interacting with IRS1 and activating the PI3K/AKT pathway.
- Triple-negative breast cancer,
- ACOT7,
- PI3K/AKT signaling pathway,
- Proliferation,
- Migration,
- Invasion

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References(23)

References

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