Original article

Forkhead box D1 promotes invasion and metastasis of pancreatic cancer via extracellular signal-regulated kinase pathway

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  • Department of Medical Oncology, The First Affiliated Hospital of Zhejiang University of Chinese Medicine, Zhejiang Hangzhou 310002, China

Received date: 2020-09-09

  Online published: 2022-07-20

Abstract

Objective To study on the expression of forkhead box D1 (FOXD1) in pancreatic cancer and the mechanism of invasion and metastasis of pancreatic cancer through FOXD1 via the extracellular signal-regulated kinase (ERK) pathway. Methods We searched the database of expression of FOXD1 in both pancreatic cancer and normal pancreatic tissue from the Cancer Genome Atlas and analyzed the difference in expression of FOXD1. Expression of FOXD1 mRNA in pancreatic tissue of 15 cases with pancreatic cancer was detected using polymerase chain reaction. Expression of FOXD1 in pancreatic cancer cell lines was analyzed using Western Blot. The effect of FOXD1 knockdown on the expression of proteins associated with epithelial mesenchymal transition(EMT) was investigated using Western Blot. The effect of FOXD1 knockdown on the proliferation and invasion of pancreatic cancer cell lines were tested by cell counting kit-8 assay and Transwell assay. Results FOXD1 was highly expressed in pancreatic cancer tissues and cell lines. Knockdown of FOXD1 attenuated the proliferation and invasion of pancreatic cancer cell lines and enhanced expression of EMT associa-ted proteins including epithelial cadherin and ERK while attenuated expression of neuronal cadherin and phosphorylated ERK. Conclusions FOXD1 would be the oncogene of pancreatic cancer by promoting invasion and metastasis of pancrea-tic cancer via ERK pathway.

Cite this article

DING Fangmi, LIU Zhendong . Forkhead box D1 promotes invasion and metastasis of pancreatic cancer via extracellular signal-regulated kinase pathway[J]. Journal of Surgery Concepts & Practice, 2020 , 25(06) : 486 -492 . DOI: 10.16139/j.1007-9610.2020.06.009

References

[1] Siegel RL, Miller KD. Cancer statistics, 2019[J]. CA Cancer J Clin, 2019, 69(1):7-34.
[2] Chen W, Zheng R, Baade PD, et al. Cancer statistics in China, 2015[J]. CA Cancer J Clin, 2016, 66(2):115-132.
[3] Pierrou S, Hellqvist M, Samuelsson L, et al. Cloning and characterization of seven human forkhead proteins: bin-ding site specificity and DNA bending[J]. EMBO J, 1994, 13(20):5002-5012.
[4] Nakayama S, Soejima K, Yasuda H, et al. FOXD1 expression is associated with poor prognosis in non-small cell lung cancer[J]. Anticancer Res, 2015, 35(1):261-268.
[5] Zhao YF, Zhao JY, Yue H, et al. FOXD1 promotes breast cancer proliferation and chemotherapeutic drug resistance by targeting p27[J]. Biochem Biophys Res Commun, 2015, 456(1):232-237.
[6] Li D, Fan S, Yu F, et al. FOXD1 promotes cell growth and metastasis by activation of vimentin in NSCLC[J]. Cell Physiol Biochem, 2018, 51(6):2716-2731.
[7] Farhan M, Wang H, Gaur U, et al. FOXO signaling pathways as therapeutic targets in cancer[J]. Int J Biol Sci, 2017, 13(7):815-827.
[8] Ernstsson S, Pierrou S, Hulander M, et al. Characterization of the human forkhead gene FREAC-4. Evidence for regulation by Wilms' tumor suppressor gene (WT-1) and p53[J]. J Biol Chem, 1996, 271(35):21094-21099.
[9] Gao YF, Liu JY, Mao XY, et al. LncRNA FOXD1-AS1 acts as a potential oncogenic biomarker in glioma[J]. CNS Neurosci Ther, 2020, 26(1):66-75.
[10] Song R, Lopez M, Yosypiv IV. Foxd1 is an upstream re-gulator of the renin-angiotensin system during metanephric kidney development[J]. Pediatr Res, 2017, 82(5):855-862.
[11] Wu Q, Ma J, Wei J, et al. FOXD1-AS1 regulates FOXD1 translation and promotes gastric cancer progression and chemoresistance by activating the PI3K/AKT/mTOR pathway[J]. Mol Oncol, 2020-05-27.[online ahead of print].
[12] Wang Y, Qiu C, Lu N, et al. FOXD1 is targeted by miR-30a-5p and miR-200a-5p and suppresses the proliferation of human ovarian carcinoma cells by promoting p21 expression in a p53-independent manner[J]. Int J Oncol, 2018, 52(6):2130-2142.
[13] Pan F, Li M, Chen W. FOXD1 predicts prognosis of co-lorectal cancer patients and promotes colorectal cancer progression via the ERK 1/2 pathway[J]. Am J Transl Res, 2018, 10(5):1522-1530.
[14] Li CH, Chang YC, Hsiao M, et al. FOXD1 and Gal-3 form a positive regulatory loop to regulate lung cancer aggressiveness[J]. Cancers (Basel), 2019, 11(12):1897-1915.
[15] Gao YF, Zhu T, Mao XY, et al. Silencing of forkhead box D1 inhibits proliferation and migration in glioma cells[J]. Oncol Rep, 2017, 37(2):1196-1202.
[16] Lamouille S, Xu J, Derynck R. Molecular mechanisms of epithelial-mesenchymal transition[J]. Nat Rev Mol Cell Biol, 2014, 15(3):178-196.
[17] Li X, Dong M, Zhou J, et al. C6orf106 accelerates pancreatic cancer cell invasion and proliferation via activa-ting ERK signaling pathway[J]. Mol Cell Biochem, 2019, 454(1-2):87-95.
[18] Qi ZH, Xu HX, Zhang SR, et al. RIPK4/PEBP1 axis promotes pancreatic cancer cell migration and invasion by activating RAF1/MEK/ERK signaling[J]. Int J Oncol, 2018, 52(4):1105-1116.
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