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Inhibition of apoptosis in breast cancer cells by si‑FoxO3a through the protein digestion and absorption signaling pathway

  • Authors:
    • Liying Sun
    • Zhongxu Wang
    • Yanxi Liu
    • Jiaxin Lv
    • Xiaotong Shao
    • Haoming Tang
    • Cheng Hu
    • Liang Cao
    • Yundong Zhao
    • Shuang Chen
  • View Affiliations / Copyright

    Affiliations: College of Laboratory Medicine, Jilin Medical University, Jilin, Jilin 132013, P.R. China, College of Medical Technology, Beihua University, Jilin, Jilin 132013, P.R. China
    Copyright: © Sun et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 599
    |
    Published online on: October 17, 2025
       https://doi.org/10.3892/ol.2025.15345
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Abstract

FoxO3a is closely associated with the occurrence and development of tumors. The present study aimed to evaluate the effect of FoxO3a on apoptosis in breast cancer, and to clarify the regulation of the protein digestion and absorption pathway in two breast cancer cell lines, through interfering with the expression of FoxO3a. MCF‑7 and MDA‑MB‑231 were selected as the focal cells to study, and small interfering (si)RNA transfection technology was used to knockdown the expression of FoxO3a in both cell types. Clinical antitumor drugs were selected to treat cancer cells transfected with negative control sequences (si‑NC) and sequences targeting FoxO3a (si‑FoxO3a) in order to determine both the number of apoptotic cells and their morphology, and to assess migration levels using a wound healing assay. The cells were divided into si‑NC and si‑FoxO3a dosing groups for proteomics analyses, which were conducted using the differentially expressed proteins (DEPs) and the common signaling pathways were investigated. Finally, key proteins were validated using western blotting. First, the baseline expression levels of FoxO3a in two types of breast cancer cells were validated, confirming the presence of FoxO3a expression in both cell types. Next, FoxO3a was knocked down. Drug concentrations of tamoxifen (25 µmol/ml) and doxorubicin (30 µmol/ml) were selected for MCF‑7 and MDA‑MB‑231 cells, respectively. si‑FoxO3a reduced tumor cell death, and the apoptosis rate of cells treated with si‑FoxO3a was notably decreased, indicated by Hoechst staining with reduced brightness. There was also a notable increase in scratch healing rate. After screening of DEPs by proteomics analysis, Gene Ontology enrichment analyses revealed common molecular functions of DEPs in both breast cancer cell lines at the cellular component and molecular function levels, predominantly extracellular space and L‑glutamine transmembrane transporter activity. Kyoto Encyclopedia of Genes and Genomes functional enrichment analysis demonstrated that the main signaling pathway involved in apoptosis of both cell lines after FoxO3a knockdown was the protein digestion and absorption pathway. Protein‑protein interaction mapping results showed a close relationship between DEPs. Focal DEPs were validated, and the findings were consistent with the proteomics results. Overall, the results demonstrated that si‑FoxO3a inhibited the apoptosis of breast cancer cells through the protein digestion and absorption signaling pathway.
View Figures

Figure 1

FoxO3a baseline level and efficiency
of interference. (A) RT-qPCR detection of MCF-7 and MDA-MB-231
FoxO3a expression, and comparison with MCF-10A cells. (B) Western
blot detection of MCF-7 and MDA-MB-231 FoxO3a expression, and
comparison with MCF-10A cells. (C) RT-qPCR detection of FoxO3a
expression level in MCF-7 cells. (D) RT-qPCR detection of FoxO3a
expression level in MDA-MB-231 cells. *P<0.05; **P<0.01;
***P<0.001. RT-qPCR, reverse transcription quantitative PCR; si,
small interfering RNA; NC, negative control.

Figure 2

Water-soluble tetrazolium salt
results and inhibitory effects of drugs on apoptosis of si-NC and
si-FoxO3a cells. (A) Inhibitory effect of different concentrations
of TAM on MCF-7 cells. (B) Inhibitory effect of different
concentrations of DOX on MDA-MB-231 cells. (C) Flow cytometry
analysis of the apoptosis rate of TAM (0 µmol/ml, 25 µmol/ml)
treated MCF-7 si-NC and si-FoxO3a cells and results of the data
analysis of apoptosis rate. (D) Flow cytometry analysis of the
apoptosis rate of DOX (0 µmol/ml, 30 µmol/ml) treated MDA-MB-231
si-NC and si-FoxO3a cells and results of the data analysis of
apoptosis rate. *P<0.05; **P<0.01; ***P<0.001. n=3, data
shown as mean ± standard deviation. si, small interfering RNA; NC,
negative control; TAM, tamoxifen; DOX, doxorubicin; PI, propidium
iodine.

Figure 3

Hoechst staining results of si-NC and
si-FoxO3a cells after drug treatment and volcano plot of
differentially expressed proteins. (A) MCF-7 si-NC and si-FoxO3a
cells without TAM treatment had no obvious apoptotic morphology.
Cells in both groups showed apoptotic morphology after TAM
treatment. Magnification, ×400. (B) MDA-MB-231 si-NC and si-FoxO3a
cells without DOX treatment had no obvious apoptotic morphology.
Cells in both groups showed apoptotic morphology after DOX
treatment. Magnification, ×400. (C) Significantly downregulated
proteins of MCF-7 cells are shown on the left side of the vertical
dashed line. Significantly upregulated proteins are shown on the
right side of the vertical dashed line. Non-significantly altered
proteins are shown in gray. (D) Significantly downregulated
proteins of MDA-MB-231 cells are shown on the left side of the
vertical dashed line. Significantly upregulated proteins are shown
on the right side of the vertical dashed line. Non-significantly
altered proteins are shown in gray. n=3, data shown as mean ±
standard deviation. *P<0.05; **P<0.01. si, small interfering
RNA; NC, negative control; TAM, tamoxifen; DOX, doxorubicin; ctrl,
control.

Figure 4

Migration of si-NC and si-FoxO3a
cells after drug treatment. (A) Effect of TAM (0 µmol/ml, 25
µmol/ml) treatment on the migratory ability of MCF-7 si-NC and
si-FoxO3a cells. (B) Effect of DOX (0 µmol/ml, 30 µmol/ml)
treatment on the migratory ability of MDA-MB-231 si-NC and
si-FoxO3a cells. *P<0.05. si, small interfering RNA; NC,
negative control; TAM, tamoxifen; DOX, doxorubicin.

Figure 5

Pie charts of subcellular
localization. (A) Pie chart of subcellular localization of
differentially expressed proteins in MCF-7 cells. (B) Pie chart of
subcellular localization of differentially expressed proteins in
MDA-MB-231 cells.

Figure 6

GO secondary classification chart.
(A) GO secondary classification bar chart of MCF-7 cells. (B) GO
secondary classification bar chart of MDA-MB-231. GO, gene
ontology.

Figure 7

KEGG secondary classification chart.
(A) Boxed out KEGG classification map representing the majority of
differentially expressed proteins in MCF-7 cells. (B) Boxed out
KEGG classification map representing the majority of differentially
expressed proteins in MDA-MB-231 cells. KEGG, Kyoto Encyclopedia of
Genes and Genomes.

Figure 8

GO enrichment analysis bubble plots
of DEPs. (A) Bubble plot of MCF-7 cells DEPs at the CC level of GO
enrichment analysis. (B) Bubble plot of MDA-MB-231 cells DEPs at
the CC level of GO enrichment analysis. (C) Bubble plot of MCF-7
cells DEPs at the MF level of GO enrichment analysis. (D) Bubble
plot of MDA-MB-231 cells DEPs at the MF level of GO enrichment
analysis. GO, gene ontology; DEPs, differentially expressed
proteins; CC, cellular component; MF, molecular function.

Figure 9

Circos plot of DEPs KEGG pathway
enrichment, interaction diagram of DEPs with FoxO3a and western
blot results. (A) Circos plot of MCF-7 cell DEPs. (B) Circos plot
of MDA-MB-231 cell DEPs. map04974 represents the protein digestion
and absorption signal pathway. (C) Protein-protein interaction
diagram of DEPs with FoxO3a. (D) The expression of DEPs in MCF-7
cells was assessed using western blotting. (E) The expression of
DEPs in MDA-MB-231 cells was verified using western blotting. DEP,
differentially expressed protein; KEGG, Kyoto Encyclopedia of Genes
and Genomes; si, small interfering RNA; NC, negative control; TPBG,
trophoblastic glycoprotein; SLC38A2, solute carrier family 38
member 2; ZYX, zyxin; ASNS, asparagine synthetase.

Figure 10

FoxO3a regulates the protein
digestion and absorption signaling pathway. Antitumor drugs act on
breast cancer cells, inducing mitochondrial damage and triggering
the internal apoptotic program of cancer cells. si-FoxO3a impedes
the mitochondrial damage process and affects Gln transport into the
cell by decreasing the expression of the amino acid transport
protein SLC38A2. This leads to a decrease in the conversion of Gln
to glutamate, a decrease in the tricarboxylic acid cycle
intermediate product OAA and the catalytic function of ASNS cannot
be effectively performed. α-KG deficiency decreases mTOR
expression. FoxO3a suppresses mTOR expression, thereby inhibiting
ZYX expression and promoting cancer cell apoptosis. FoxO3 also
affects TPBG levels through regulation of the Wnt signaling pathway
to promote apoptosis in cancer cells. si, small interfering;
SLC38A2, solute carrier family 38 member 2; ASNS, asparagine
synthetase; α-KG, α-ketoglutarate; mTOR, mechanistic target of
rapamycin kinase; TPBG, trophoblastic glycoprotein; ZYX, zyxin;
Gluo, glutamate dehydrogenase; OAA, oxaloacetic acid; GS, glutamine
synthetase.
View References

1 

Katsura C, Ogunmwonyi I, Kankam HK and Saha S: Breast cancer: Presentation, investigation and management. Br J Hosp Med (Lond). 83:1–7. 2022. View Article : Google Scholar : PubMed/NCBI

2 

Avti PK, Singh J, Dahiya D and Khanduja KL: Dual functionality of pyrimidine and flavone in targeting genomic variants of EGFR and ER receptors to influence the differential survival rates in breast cancer patients. Integr Biol (Camb). 15:zyad0142023. View Article : Google Scholar : PubMed/NCBI

3 

Fortin J, Leblanc M, Elgbeili G, Cordova MJ, Marin MF and Brunet A: The mental health impacts of receiving a breast cancer diagnosis: A meta-analysis. Br J Cancer. 125:1582–1592. 2021. View Article : Google Scholar : PubMed/NCBI

4 

Ye F, Dewanjee S, Li Y, Jha NK, Chen ZS, Kumar A, Vishakha Behl T, Jha SK and Tang H: Advancements in clinical aspects of targeted therapy and immunotherapy in breast cancer. Mol Cancer. 22:1052023. View Article : Google Scholar : PubMed/NCBI

5 

Castellote-Huguet P, Ruiz-Espana S, Galan-Auge C, Santabarbara JM, Maceira AM and Moratal D: Breast cancer diagnosis using texture and shape features in MRI. Annu Int Conf IEEE Eng Med Biol Soc. 2023:1–4. 2023. View Article : Google Scholar

6 

Nunnery SE and Mayer IA: Targeting the PI3K/AKT/mTOR pathway in hormone-positive breast cancer. Drugs. 80:1685–1697. 2020. View Article : Google Scholar : PubMed/NCBI

7 

Kotsopoulos J, Gronwald J, Huzarski T, Aeilts A, Armel SR, Karlan B, Singer CF, Eisen A, Tung N, Olopade O, et al: Tamoxifen and the risk of breast cancer in women with a BRCA1 or BRCA2 mutation. Breast Cancer Res Treat. 201:257–264. 2023. View Article : Google Scholar

8 

Masci D, Naro C, Puxeddu M, Urbani A, Sette C, La Regina G and Silvestri R: Recent advances in drug discovery for triple-negative breast cancer treatment. Molecules. 28:75132023. View Article : Google Scholar : PubMed/NCBI

9 

Xu C, Feng Q, Yang H, Wang G, Huang L, Bai Q, Zhang C, Wang Y, Chen Y, Cheng Q, et al: A light-triggered mesenchymal stem cell delivery system for photoacoustic imaging and chemo-photothermal therapy of triple negative breast cancer. Adv Sci (Weinh). 5:18003822018. View Article : Google Scholar : PubMed/NCBI

10 

Hwang KT, Kim J, Jung J, Chang JH, Chai YJ, Oh SW, Oh S, Kim YA, Park SB and Hwang KR: Impact of breast cancer subtypes on prognosis of women with operable invasive breast cancer: A population-based study using SEER database. Clin Cancer Res. 25:1970–1979. 2019. View Article : Google Scholar : PubMed/NCBI

11 

Al-Azhri J, Zhang Y, Bshara W, Zirpoli G, McCann SE, Khoury T, Morrison CD, Edge SB, Ambrosone CB and Yao S: Tumor expression of vitamin D receptor and breast cancer histopathological characteristics and prognosis. Clin Cancer Res. 23:97–103. 2017. View Article : Google Scholar : PubMed/NCBI

12 

Sun Z, Zhou D, Yang J and Zhang D: Doxorubicin promotes breast cancer cell migration and invasion via DCAF13. FEBS Open Bio. 12:221–230. 2022. View Article : Google Scholar : PubMed/NCBI

13 

Jiang D, Qiu T, Peng J, Li S, Tala Ren W, Yang C, Wen Y, Chen CH, Sun J, et al: YB-1 is a positive regulator of KLF5 transcription factor in basal-like breast cancer. Cell Death Differ. 29:1283–1295. 2022. View Article : Google Scholar : PubMed/NCBI

14 

Katzenellenbogen BS, Guillen VS and Katzenellenbogen JA: Targeting the oncogenic transcription factor FOXM1 to improve outcomes in all subtypes of breast cancer. Breast Cancer Res. 25:762023. View Article : Google Scholar : PubMed/NCBI

15 

Francois M, Donovan P and Fontaine F: Modulating transcription factor activity: Interfering with protein-protein interaction networks. Semin Cell Dev Biol. 99:12–19. 2020. View Article : Google Scholar

16 

Liu TT, Yang H, Zhuo FF, Yang Z, Zhao MM, Guo Q, Liu Y, Liu D, Zeng KW and Tu PF: Atypical E3 ligase ZFP91 promotes small-molecule-induced E2F2 transcription factor degradation for cancer therapy. EBioMedicine. 86:1043532022. View Article : Google Scholar : PubMed/NCBI

17 

Pang X, Zhou Z, Yu Z, Han L, Lin Z, Ao X, Liu C, He Y, Ponnusamy M, Li P and Wang J: Foxo3a-dependent miR-633 regulates chemotherapeutic sensitivity in gastric cancer by targeting Fas-associated death domain. RNA Biol. 16:233–248. 2019. View Article : Google Scholar

18 

Meng XY, Wang KJ, Ye SZ, Chen JF, Chen ZY, Zhang ZY, Yin WQ, Jia XL, Li Y, Yu R and Ma Q: Sinularin stabilizes FOXO3 protein to trigger prostate cancer cell intrinsic apoptosis. Biochem Pharmacol. 220:1160112024. View Article : Google Scholar

19 

Khoshinani HM, Afshar S, Pashaki AS, Mahdavinezhad A, Nikzad S, Najafi R, Amini R, Gholami MH, Khoshghadam A and Saidijam M: Involvement of miR-155/FOXO3a and miR-222/PTEN in acquired radioresistance of colorectal cancer cell line. Jpn J Radiol. 35:664–672. 2017. View Article : Google Scholar

20 

Wolfe AR, Debeb BG, Lacerda L, Larson R, Bambhroliya A, Huang X, Bertucci F, Finetti P, Birnbaum D, Van Laere S, et al: Simvastatin prevents triple-negative breast cancer metastasis in pre-clinical models through regulation of FOXO3a. Breast Cancer Res Treat. 154:495–508. 2015. View Article : Google Scholar

21 

Chen S, Li YQ, Yin XZ, Li SZ, Zhu YL, Fan YY, Li WJ, Cui YL, Zhao J, Li X, et al: Recombinant adenoviruses expressing apoptin suppress the growth of MCF-7 breast cancer cells and affect cell autophagy. Oncol Rep. 41:2818–2832. 2019.PubMed/NCBI

22 

Kang BG, Shende M, Inci G, Park SH, Jung JS, Kim SB, Kim JH, Mo YW, Seo JH, Feng JH, et al: Combination of metformin/efavirenz/fluoxetine exhibits profound anticancer activity via a cancer cell-specific ROS amplification. Cancer Biol Ther. 24:20–32. 2023.PubMed/NCBI

23 

Schmittgen TD and Livak KJ: Analyzing real-time PCR data by the comparative C(T) method. Nat Protoc. 3:1101–1108. 2008. View Article : Google Scholar

24 

Khan MA, Sadaf Ahmad I, Aloliqi AA, Eisa AA, Najm MZ, Habib M, Mustafa S, Massey S, Malik Z, et al: FOXO3 gene hypermethylation and its marked downregulation in breast cancer cases: A study on female patients. Front Oncol. 12:10780512022. View Article : Google Scholar

25 

Yang L, Zhang Y, Zhang Y, Xu Y, Li Y, Xie Z, Wang H, Lin Y, Lin Q, Gong T, et al: Live macrophage-delivered doxorubicin-loaded liposomes effectively treat triple-negative breast cancer. ACS Nano. 16:9799–9809. 2022. View Article : Google Scholar : PubMed/NCBI

26 

Ansari L, Shiehzadeh F, Taherzadeh Z, Nikoofal-Sahlabadi S, Momtazi-Borojeni AA, Sahebkar A and Eslami S: The most prevalent side effects of pegylated liposomal doxorubicin monotherapy in women with metastatic breast cancer: A systematic review of clinical trials. Cancer Gene Ther. 24:189–193. 2017. View Article : Google Scholar : PubMed/NCBI

27 

Wei Y, Guo Y, Zhou J, Dai K, Xu Q and Jin X: Nicotinamide overcomes doxorubicin resistance of breast cancer cells through deregulating SIRT1/Akt pathway. Anticancer Agents Med Chem. 19:687–696. 2019. View Article : Google Scholar : PubMed/NCBI

28 

Sun L, Liu J, Bao D, Hu C, Zhao Y and Chen S: Progress in the study of FOXO3a interacting with microRNA to regulate tumourigenesis development. Front Oncol. 13:12939682023. View Article : Google Scholar

29 

Chen YF, Pandey S, Day CH, Chen YF, Jiang AZ, Ho TJ, Chen RJ, Padma VV, Kuo WW and Huang CY: Synergistic effect of HIF-1α and FoxO3a trigger cardiomyocyte apoptosis under hyperglycemic ischemia condition. J Cell Physiol. 233:3660–3671. 2018. View Article : Google Scholar

30 

Yadav RK, Chauhan AS, Zhuang L and Gan B: FoxO transcription factors in cancer metabolism. Semin Cancer Biol. 50:65–76. 2018. View Article : Google Scholar

31 

Liu H, Yin J, Wang H, Jiang G, Deng M, Zhang G, Bu X, Cai S, Du J and He Z: FOXO3a modulates WNT/β-catenin signaling and suppresses epithelial-to-mesenchymal transition in prostate cancer cells. Cell Signal. 27:510–518. 2015. View Article : Google Scholar

32 

Li H, Tang X, Sun Z, Qu Z and Zou X: Integrating bioinformatics and experimental models to investigate the mechanism of the chelidonine-induced mitotic catastrophe via the AKT/FOXO3/FOXM1 axis in breast cancer cells. Biomol Biomed. 24:560–574. 2024. View Article : Google Scholar : PubMed/NCBI

33 

Gauthier-Coles G, Bröer A, McLeod MD, George AJ, Hannan RD and Bröer S: Identification and characterization of a novel SNAT2 (SLC38A2) inhibitor reveals synergy with glucose transport inhibition in cancer cells. Front Pharmacol. 13:9630662022. View Article : Google Scholar

34 

Petry ÉR, Dresch DF, Carvalho C, Medeiros PC, Rosa TG, de Oliveira CM, Martins LAM, Guma FCR, Marroni NP and Wannmacher CMD: Oral glutamine supplementation relieves muscle loss in immobilized rats, altering p38MAPK and FOXO3a signaling pathways. Nutrition. 118:1122732024. View Article : Google Scholar : PubMed/NCBI

35 

Yuan Q, Wang Q, Li J, Yin L, Liu S, Zu X and Shen Y: CCT196969 inhibits TNBC by targeting the HDAC5/RXRA/ASNS axis to down-regulate asparagine synthesis. J Exp Clin Cancer Res. 44:2312025. View Article : Google Scholar : PubMed/NCBI

36 

Zhao X, Lai H, Li G, Qin Y, Chen R, Labrie M, Stommel JM, Mills GB, Ma D, Gao Q and Fang Y: Rictor orchestrates β-catenin/FOXO balance by maintaining redox homeostasis during development of ovarian cancer. Oncogene. 44:1820–1832. 2025. View Article : Google Scholar : PubMed/NCBI

37 

Park S, Yoo JE, Yeon GB, Kim JH, Lee JS, Choi SK, Hwang YG, Park CW, Cho MS, Kim J, et al: Trophoblast glycoprotein is a new candidate gene for Parkinson's disease. NPJ Parkinsons Dis. 7:1102021. View Article : Google Scholar : PubMed/NCBI

38 

He P, Jiang S, Ma M, Wang Y, Li R, Fang F, Tian G and Zhang Z: Trophoblast glycoprotein promotes pancreatic ductal adenocarcinoma cell metastasis through Wnt/planar cell polarity signaling. Mol Med Rep. 12:503–509. 2015. View Article : Google Scholar : PubMed/NCBI

39 

Su H, Yu S, Sun F, Lin D, Liu P and Zhao L: LINC00342 induces metastasis of lung adenocarcinoma by targeting miR-15b/TPBG. Acta Biochim Pol. 69:291–297. 2022.

40 

Ye F, Liang Y, Wang Y, Yang RL, Luo D, Li Y, Jin Y, Han D, Chen B, Zhao W, et al: Cancer-associated fibroblasts facilitate breast cancer progression through exosomal circTBPL1-mediated intercellular communication. Cell Death Dis. 14:4712023. View Article : Google Scholar : PubMed/NCBI

41 

Hu G, Leal M, Lin Q, Affolter T, Sapra P, Bates B and Damelin M: Phenotype of TPBG gene replacement in the mouse and impact on the pharmacokinetics of an antibody-drug conjugate. Mol Pharm. 12:1730–1737. 2015. View Article : Google Scholar : PubMed/NCBI

42 

Stern PL, Brazzatti J, Sawan S and McGinn OJ: Understanding and exploiting 5T4 oncofoetal glycoprotein expression. Semin Cancer Biol. 29:13–20. 2014. View Article : Google Scholar

43 

Kandasamy P, Zlobec I, Nydegger DT, Pujol-Giménez J, Bhardwaj R, Shirasawa S, Tsunoda T and Hediger MA: Oncogenic KRAS mutations enhance amino acid uptake by colorectal cancer cells via the hippo signaling effector YAP1. Mol Oncol. 15:2782–2800. 2021. View Article : Google Scholar

44 

Kandasamy P, Gyimesi G, Kanai Y and Hediger MA: Amino acid transporters revisited: New views in health and disease. Trends Biochem Sci. 43:752–789. 2018. View Article : Google Scholar

45 

Morotti M, Zois CE, El-Ansari R, Craze ML, Rakha EA, Fan SJ, Valli A, Haider S, Goberdhan DCI, Green AR and Harris AL: Increased expression of glutamine transporter SNAT2/SLC38A2 promotes glutamine dependence and oxidative stress resistance, and is associated with worse prognosis in triple-negative breast cancer. Br J Cancer. 124:494–505. 2021. View Article : Google Scholar : PubMed/NCBI

46 

Morotti M, Bridges E, Valli A, Choudhry H, Sheldon H, Wigfield S, Gray N, Zois CE, Grimm F, Jones D, et al: Hypoxia-induced switch in SNAT2/SLC38A2 regulation generates endocrine resistance in breast cancer. Proc Natl Acad Sci USA. 116:12452–12461. 2019. View Article : Google Scholar : PubMed/NCBI

47 

Stretton C, Lipina C, Hyde R, Cwiklinski E, Hoffmann TM, Taylor PM and Hundal HS: CDK7 is a component of the integrated stress response regulating SNAT2 (SLC38A2)/System A adaptation in response to cellular amino acid deprivation. Biochim Biophys Acta Mol Cell Res. 1866:978–991. 2019. View Article : Google Scholar : PubMed/NCBI

48 

Shen Y, Li M, Xiong Y, Gui S, Bai J, Zhang Y and Li C: Proteomics analysis identified ASNS as a novel biomarker for predicting recurrence of skull base chordoma. Front Oncol. 11:6984972021. View Article : Google Scholar

49 

Du F, Chen J, Liu H, Cai Y, Cao T, Han W, Yi X, Qian M, Tian D, Nie Y, et al: SOX12 promotes colorectal cancer cell proliferation and metastasis by regulating asparagine synthesis. Cell Death Dis. 10:2392019. View Article : Google Scholar : PubMed/NCBI

50 

Knott SRV, Wagenblast E, Khan S, Kim SY, Soto M, Wagner M, Turgeon MO, Fish L, Erard N, Gable AL, et al: Asparagine bioavailability governs metastasis in a model of breast cancer. Nature. 554:378–381. 2018. View Article : Google Scholar : PubMed/NCBI

51 

Yang H, He X, Zheng Y, Feng W, Xia X, Yu X and Lin Z: Down-regulation of asparagine synthetase induces cell cycle arrest and inhibits cell proliferation of breast cancer. Chem Biol Drug Des. 84:578–584. 2014. View Article : Google Scholar : PubMed/NCBI

52 

Qin C, Yang X and Zhan Z: High expression of asparagine synthetase is associated with poor prognosis of breast cancer in Chinese population. Cancer Biother Radiopharm. 35:581–585. 2020. View Article : Google Scholar : PubMed/NCBI

53 

Nishikawa G, Kawada K, Hanada K, Maekawa H, Itatani Y, Miyoshi H, Taketo MM and Obama K: Targeting asparagine synthetase in tumorgenicity using patient-derived tumor-initiating cells. Cells. 11:32732022. View Article : Google Scholar : PubMed/NCBI

54 

Chen W, Qin Y, Qiao L, Liu X, Gao C, Li TR, Luo Y, Li D, Yan H, Han L, et al: FAM50A drives breast cancer brain metastasis through interaction with C9ORF78 to enhance L-asparagine production. Sci Adv. 11:eadt30752025. View Article : Google Scholar : PubMed/NCBI

55 

Reis LMD, Adamoski D, Souza RO, Ascenção CF, de Oliveira KR, Corrêa-da-Silva F, de Sá, Patroni FM, Dias MM, Consonni SR, de Moraes-Vieira PMM, et al: Dual inhibition of glutaminase and carnitine palmitoyltransferase decreases growth and migration of glutaminase inhibition-resistant triple-negative breast cancer cells. J Biol Chem. 294:9342–9357. 2019. View Article : Google Scholar : PubMed/NCBI

56 

Partynska A, Gomulkiewicz A, Dziegiel P and Podhorska-Okolow M: The role of zyxin in carcinogenesis. Anticancer Res. 40:5981–5988. 2020. View Article : Google Scholar : PubMed/NCBI

57 

Kotb A, Hyndman ME and Patel TR: The role of zyxin in regulation of malignancies. Heliyon. 4:e006952018. View Article : Google Scholar : PubMed/NCBI

58 

Cai T, Bai J, Tan P, Huang Z, Liu C, Wu Z, Cheng Y, Li T, Chen Y, Ruan J, et al: Zyxin promotes hepatocellular carcinoma progression via the activation of AKT/mTOR signaling pathway. Oncol Res. 31:805–817. 2023. View Article : Google Scholar : PubMed/NCBI

59 

Mohammadi H, Shakiba E, Rostampour R, Bahremand K, Goodarzi MT, Bashiri H, Ghobadi KN and Asadi S: Down expression of zyxin is associated with down expression of p53 in colorectal cancer. Int J Mol Cell Med. 14:461–471. 2025.PubMed/NCBI

60 

Ma B, Cheng H, Gao R, Mu C, Chen L, Wu S, Chen Q and Zhu Y: Zyxin-Siah2-Lats2 axis mediates cooperation between Hippo and TGF-β signalling pathways. Nat Commun. 7:111232016. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Sun L, Wang Z, Liu Y, Lv J, Shao X, Tang H, Hu C, Cao L, Zhao Y, Chen S, Chen S, et al: Inhibition of apoptosis in breast cancer cells by si‑FoxO3a through the protein digestion and absorption signaling pathway. Oncol Lett 30: 599, 2025.
APA
Sun, L., Wang, Z., Liu, Y., Lv, J., Shao, X., Tang, H. ... Chen, S. (2025). Inhibition of apoptosis in breast cancer cells by si‑FoxO3a through the protein digestion and absorption signaling pathway. Oncology Letters, 30, 599. https://doi.org/10.3892/ol.2025.15345
MLA
Sun, L., Wang, Z., Liu, Y., Lv, J., Shao, X., Tang, H., Hu, C., Cao, L., Zhao, Y., Chen, S."Inhibition of apoptosis in breast cancer cells by si‑FoxO3a through the protein digestion and absorption signaling pathway". Oncology Letters 30.6 (2025): 599.
Chicago
Sun, L., Wang, Z., Liu, Y., Lv, J., Shao, X., Tang, H., Hu, C., Cao, L., Zhao, Y., Chen, S."Inhibition of apoptosis in breast cancer cells by si‑FoxO3a through the protein digestion and absorption signaling pathway". Oncology Letters 30, no. 6 (2025): 599. https://doi.org/10.3892/ol.2025.15345
Copy and paste a formatted citation
x
Spandidos Publications style
Sun L, Wang Z, Liu Y, Lv J, Shao X, Tang H, Hu C, Cao L, Zhao Y, Chen S, Chen S, et al: Inhibition of apoptosis in breast cancer cells by si‑FoxO3a through the protein digestion and absorption signaling pathway. Oncol Lett 30: 599, 2025.
APA
Sun, L., Wang, Z., Liu, Y., Lv, J., Shao, X., Tang, H. ... Chen, S. (2025). Inhibition of apoptosis in breast cancer cells by si‑FoxO3a through the protein digestion and absorption signaling pathway. Oncology Letters, 30, 599. https://doi.org/10.3892/ol.2025.15345
MLA
Sun, L., Wang, Z., Liu, Y., Lv, J., Shao, X., Tang, H., Hu, C., Cao, L., Zhao, Y., Chen, S."Inhibition of apoptosis in breast cancer cells by si‑FoxO3a through the protein digestion and absorption signaling pathway". Oncology Letters 30.6 (2025): 599.
Chicago
Sun, L., Wang, Z., Liu, Y., Lv, J., Shao, X., Tang, H., Hu, C., Cao, L., Zhao, Y., Chen, S."Inhibition of apoptosis in breast cancer cells by si‑FoxO3a through the protein digestion and absorption signaling pathway". Oncology Letters 30, no. 6 (2025): 599. https://doi.org/10.3892/ol.2025.15345
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