LPCAT1 is transcriptionally regulated by FOXA1 to promote breast cancer progression and paclitaxel resistance

Zhang,Huayi; Zheng,Yaqin

doi:10.3892/ol.2023.13720

LPCAT1 is transcriptionally regulated by FOXA1 to promote breast cancer progression and paclitaxel resistance

Authors:
- Huayi Zhang
- Yaqin Zheng
View Affiliations

Affiliations: Department of Breast Surgery, Shanxi Provincial Cancer Hospital, Taiyuan, Shanxi 030013, P.R. China, Department of Radiation Oncology, Shanxi Provincial Cancer Hospital, Taiyuan, Shanxi 030013, P.R. China
Published online on: February 15, 2023 https://doi.org/10.3892/ol.2023.13720
Article Number: 134
Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Bioinformatics analysis indicates that lysophosphatidylcholine acyltransferase 1 (LPCAT1) and forkhead box A1 (FOXA1) are highly expressed in breast cancer tissues and their expression levels are correlated. Therefore, the aim of the present study was to investigate their involvement in the malignant progression and drug resistance of breast cancer. The clinical significance of LPCAT1 was analyzed using The Cancer Genome Atlas data. The enrichment of LPCAT1 in breast cancer cells was determined and the effects of LPCAT1 knockdown on cell proliferation, colony formation, migration, invasion and paclitaxel (PTX) resistance were evaluated. The association between LPCAT1 and FOXA1 was verified using luciferase reporter and chromatin immunoprecipitation assays. Thereafter, the ability of FOXA1 overexpression to regulate LPCAT1 regulation was evaluated. The results revealed that a high LPCAT1 level was associated with poor overall survival in patients with breast cancer. Furthermore, LPCAT1 was found to be highly expressed in breast cancer cells, and its knockdown resulted in suppressed proliferation, colony formation, migration and invasion, and weakened PTX resistance. Furthermore, FOXA1 overexpression attenuated the effects of LPCAT1 knockdown on cells, indicating that FOXA1 transcriptionally regulates LPCAT1. In summary, the present study reveals that LPCAT1 is transcriptionally regulated by FOXA1, which influences breast cancer cell proliferation, metastatic potential and PTX resistance.

View Figures

View References

1	Siegel RL, Miller KD, Fuchs HE and Jemal A: Cancer statistics, 2021. CA Cancer J Clin. 71:7–33. 2021. View Article : Google Scholar : PubMed/NCBI
2	Fisusi FA and Akala EO: Drug combinations in breast cancer therapy. Pharm Nanotechnol. 7:3–23. 2019. View Article : Google Scholar : PubMed/NCBI
3	McDonald ES, Clark AS, Tchou J, Zhang P and Freedman GM: Clinical diagnosis and management of breast cancer. J Nucl Med. 57 (Suppl 1):9S–16S. 2016. View Article : Google Scholar : PubMed/NCBI
4	Sharma R, Sharma R, Khaket TP, Dutta C, Chakraborty B and Mukherjee TK: Breast cancer metastasis: Putative therapeutic role of vascular cell adhesion molecule-1. Cell Oncol (Dordr). 40:199–208. 2017. View Article : Google Scholar : PubMed/NCBI
5	Rashid NS, Grible JM, Clevenger CV and Harrell JC: Breast cancer liver metastasis: Current and future treatment approaches. Clin Exp Metastasis. 38:263–277. 2021. View Article : Google Scholar : PubMed/NCBI
6	Sugie T: Immunotherapy for metastatic breast cancer. Chin Clin Oncol. 7:282018. View Article : Google Scholar : PubMed/NCBI
7	Abu Samaan TM, Samec M, Liskova A, Kubatka P and Büsselberg D: Paclitaxel's mechanistic and clinical effects on breast cancer. Biomolecules. 9:7892019. View Article : Google Scholar : PubMed/NCBI
8	Chi Y, Xue J, Huang S, Xiu B, Su Y, Wang W, Guo R, Wang L, Li L, Shao Z, et al: CapG promotes resistance to paclitaxel in breast cancer through transactivation of PIK3R1/P50. Theranostics. 9:6840–6855. 2019. View Article : Google Scholar : PubMed/NCBI
9	AlFakeeh A and Brezden-Masley C: Overcoming endocrine resistance in hormone receptor-positive breast cancer. Curr Oncol. 25 (Suppl 1):S18–S27. 2018. View Article : Google Scholar : PubMed/NCBI
10	Jia ZH, Wang XG and Zhang H: Overcome cancer drug resistance by targeting epigenetic modifications of centrosome. Cancer Drug Resist. 2:210–224. 2019.PubMed/NCBI
11	Bi J, Ichu TA, Zanca C, Yang H, Zhang W, Gu Y, Chowdhry S, Reed A, Ikegami S, Turner KM, et al: Oncogene amplification in growth factor signaling pathways renders cancers dependent on membrane lipid remodeling. Cell Metab. 30:525–538.e8. 2019. View Article : Google Scholar : PubMed/NCBI
12	Huang Y, Wang Y, Wang Y, Wang N, Duan Q, Wang S, Liu M, Bilal MA and Zheng Y: LPCAT1 promotes cutaneous squamous cell carcinoma via EGFR-mediated protein kinase B/p38MAPK signaling pathways. J Invest Dermatol. 142:303–313.e9. 2022. View Article : Google Scholar : PubMed/NCBI
13	He RQ, Li JD, Du XF, Dang YW, Yang LJ, Huang ZG, Liu LM, Liao LF, Yang H and Chen G: LPCAT1 overexpression promotes the progression of hepatocellular carcinoma. Cancer Cell Int. 21:4422021. View Article : Google Scholar : PubMed/NCBI
14	Zhao T, Zhang Y, Ma X, Wei L, Hou Y, Sun R and Jiang J: Elevated expression of LPCAT1 predicts a poor prognosis and is correlated with the tumour microenvironment in endometrial cancer. Cancer Cell Int. 21:2692021. View Article : Google Scholar : PubMed/NCBI
15	Chandrashekar DS, Bashel B, Balasubramanya SAH, Creighton CJ, Ponce-Rodriguez I, Chakravarthi BVSK and Varambally S: UALCAN: A portal for facilitating tumor subgroup gene expression and survival analyses. Neoplasia. 19:649–658. 2017. View Article : Google Scholar : PubMed/NCBI
16	Tang Z, Li C, Kang B, Gao G, Li C and Zhang Z: GEPIA: A web server for cancer and normal gene expression profiling and interactive analyses. Nucleic Acids Res. 45((W1)): W98–W102. 2017. View Article : Google Scholar : PubMed/NCBI
17	Hu H, Miao YR, Jia LH, Yu QY, Zhang Q and Guo AY: AnimalTFDB 3.0: A comprehensive resource for annotation and prediction of animal transcription factors. Nucleic Acids Res. 47(D1): D33–D38. 2019. View Article : Google Scholar : PubMed/NCBI
18	Wang Y, Wu N, Zhang J, Wang H and Men X: MiR-153-5p enhances the sensitivity of triple-negative breast cancer cells to paclitaxel by inducing G2M phase arrest. Onco Targets Ther. 13:4089–4097. 2020. View Article : Google Scholar : PubMed/NCBI
19	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
20	Verco S, Maulhardt H, Baltezor M, Williams E, Iacobucci M, Wendt A, Verco J, Marin A, Campbell S, Dorman P and diZerega G: Local administration of submicron particle paclitaxel to solid carcinomas induces direct cytotoxicity and immune-mediated tumoricidal effects without local or systemic toxicity: Preclinical and clinical studies. Drug Deliv Transl Res. 11:1806–1817. 2021. View Article : Google Scholar : PubMed/NCBI
21	Dan VM, Raveendran RS and Baby S: Resistance to intervention: Paclitaxel in breast cancer. Mini Rev Med Chem. 21:1237–1268. 2021. View Article : Google Scholar : PubMed/NCBI
22	Mishra A, Srivastava A, Pateriya A, Tomar MS, Mishra AK and Shrivastava A: Metabolic reprograming confers tamoxifen resistance in breast cancer. Chem Biol Interact. 347:1096022021. View Article : Google Scholar : PubMed/NCBI
23	Zhang Z, Li Z, Deng M, Liu B, Xin X, Zhao Z, Zhang Y and Lv Q: Downregulation of GPSM2 is associated with primary resistance to paclitaxel in breast cancer. Oncol Rep. 43:965–974. 2020.PubMed/NCBI
24	Ge X, Cao Z, Gu Y, Wang F, Li J, Han M, Xia W, Yu Z and Lyu P: PFKFB3 potentially contributes to paclitaxel resistance in breast cancer cells through TLR4 activation by stimulating lactate production. Cell Mol Biol (Noisy-le-grand). 62:119–125. 2016.PubMed/NCBI
25	Nedeljković M and Damjanović A: Mechanisms of chemotherapy resistance in triple-negative breast cancer-how we can rise to the challenge. Cells. 8:9572019. View Article : Google Scholar : PubMed/NCBI
26	Wang B and Tontonoz P: Phospholipid remodeling in physiology and disease. Annu Rev Physiol. 81:165–188. 2019. View Article : Google Scholar : PubMed/NCBI
27	Tao M, Luo J, Gu T, Yu X, Song Z, Jun Y, Gu H, Han K, Huang X, Yu W, et al: LPCAT1 reprogramming cholesterol metabolism promotes the progression of esophageal squamous cell carcinoma. Cell Death Dis. 12:8452021. View Article : Google Scholar : PubMed/NCBI
28	Xie H, Xiao R, He Y, He L, Xie C, Chen J and Hong Y: MicroRNA-100 inhibits breast cancer cell proliferation, invasion and migration by targeting FOXA1. Oncol Lett. 22:8162021. View Article : Google Scholar : PubMed/NCBI
29	Zhu L, Wang F, Fan W, Jin Z, Teng C and Zhang J: lncRNA NEAT1 promotes the Taxol resistance of breast cancer via sponging the miR-23a-3p-FOXA1 axis. Acta Biochim Biophys Sin (Shanghai). 53:1198–1206. 2021. View Article : Google Scholar : PubMed/NCBI
30	Adams EJ, Karthaus WR, Hoover E, Liu D, Gruet A, Zhang Z, Cho H, DiLoreto R, Chhangawala S, Liu Y, et al: FOXA1 mutations alter pioneering activity, differentiation and prostate cancer phenotypes. Nature. 571:408–412. 2019. View Article : Google Scholar : PubMed/NCBI
31	Parolia A, Cieslik M, Chu SC, Xiao L, Ouchi T, Zhang Y, Wang X, Vats P, Cao X, Pitchiaya S, et al: Distinct structural classes of activating FOXA1 alterations in advanced prostate cancer. Nature. 571:413–418. 2019. View Article : Google Scholar : PubMed/NCBI
32	Arruabarrena-Aristorena A, Maag JLV, Kittane S, Cai Y, Karthaus WR, Ladewig E, Park J, Kannan S, Ferrando L, Cocco E, et al: FOXA1 mutations reveal distinct chromatin profiles and influence therapeutic response in breast cancer. Cancer Cell. 38:534–550.e9. 2020. View Article : Google Scholar : PubMed/NCBI
33	He Y, Wang L, Wei T, Xiao YT, Sheng H, Su H, Hollern DP, Zhang X, Ma J, Wen S, et al: FOXA1 overexpression suppresses interferon signaling and immune response in cancer. J Clin Invest. 131:e1470252021. View Article : Google Scholar : PubMed/NCBI