Placenta‑specific 8 is a potential novel target for osimertinib resistance in non‑small cell lung cancer

Fei,Xiaoyun; Wang,Gang; Shen,Hui; Gu,Xiaohua

doi:10.3892/ol.2019.10344

Placenta‑specific 8 is a potential novel target for osimertinib resistance in non‑small cell lung cancer

Authors:
- Xiaoyun Fei
- Gang Wang
- Hui Shen
- Xiaohua Gu
View Affiliations

Affiliations: Department of Respiratory Medicine, Shanghai Jiaotong University Affiliated Sixth People's Hospital, Shanghai 200233, P.R. China, State Key Laboratory of Bioreactor Engineering, School of Biotechnology, East China University of Science and Technology, Shanghai 200233, P.R. China
Published online on: May 13, 2019 https://doi.org/10.3892/ol.2019.10344
Pages: 955-961
Copyright: © Fei 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

Currently, osimertinib (AZD9291) is the only third‑generation epidermal growth factor receptor (EGFR)‑tyrosine kinase inhibitor approved by the Food and Drug Administration for the treatment of non‑small cell lung cancer (NSCLC) with EGFR T790M mutations. However, acquired resistance is an inevitable clinical challenge. Although placenta‑specific 8 (PLAC8) has been proven to serve an important role in tumor progression and resistance, its effect in AZD9291 resistance in NSCLC remains largely unknown. The aim of the present study was to investigate the functional role of PLAC8 in AZD9291 resistance in NSCLC. The results revealed that the level of PLAC8 was significantly upregulated in AZD9291‑resistant cells compared with that in parent cells. Overexpression of PLAC8 in parent cells markedly decreased drug sensitivity, and enhanced cell proliferation, colony formation and migration. Furthermore, the levels of aldehyde dehydrogenase 1 family member A1 (ALDH1A1) were observed to be upregulated in resistant cells and PLAC8‑overexpressing parent cells, suggesting that ALDH1A1 may be involved in the association between the overexpression of PLAC8 and AZD9291 resistance in NSCLC. Overall, PLAC8 overexpression promoted NSCLC resistance to AZD9291, and PLAC8 may be a potential target for the reversal of AZD9291 resistance.

View Figures

View References

1	Heigener DF and Reck M: Lung cancer in 2017: Giant steps and stumbling blocks. Nat Rev Clin Oncol. 15:71–72. 2018. View Article : Google Scholar : PubMed/NCBI
2	Nagasaka M and Gadgeel SM: Role of chemotherapy and targeted therapy in early-stage non-small cell lung cancer. Expert Rev Anticancer Ther. 18:63–70. 2018. View Article : Google Scholar : PubMed/NCBI
3	Mayekar MK and Bivona TG: Current landscape of targeted therapy in lung cancer. Clin Pharmacol Ther. 102:757–764. 2017. View Article : Google Scholar : PubMed/NCBI
4	Saad N, Poudel A, Basnet A and Gajra A: Epidermal growth factor receptor T790M mutation-positive metastatic non-small-cell lung cancer: Focus on osimertinib (AZD9291). Onco Targets Ther. 10:1757–1766. 2017. View Article : Google Scholar : PubMed/NCBI
5	Jänne PA, Yang JC, Kim DW, Planchard D, Ohe Y, Ramalingam SS, Ahn MJ, Kim SW, Su WC, Horn L, et al: AZD9291 in EGFR inhibitor-resistant non-small-cell lung cancer. N Engl J Med. 372:1689–1699. 2015. View Article : Google Scholar : PubMed/NCBI
6	Thress KS, Paweletz CP, Felip E, Cho BC, Stetson D, Dougherty B, Lai Z, Markovets A, Vivancos A, Kuang Y, et al: Acquired EGFR C797S mutation mediates resistance to AZD9291 in non-small cell lung cancer harboring EGFR T790M. Nat Med. 21:560–562. 2015. View Article : Google Scholar : PubMed/NCBI
7	Jimenez-Preitner M, Berney X, Uldry M, Vitali A, Cinti S, Ledford JG and Thorens B: Plac8 is an inducer of C/EBPβ required for brown fat differentiation, thermoregulation, and control of body weight. Cell Metab. 14:658–670. 2011. View Article : Google Scholar : PubMed/NCBI
8	Li Q, Lu TF, Liu D, Hu PF, Sun B, Ma JZ, Wang WJ, Wang KF, Zhang WX, Chen J, et al: Screening and analyzing genes associated with Amur tiger placental development. Genet Mol Res. 13:7869–7878. 2014. View Article : Google Scholar : PubMed/NCBI
9	Kaistha BP, Lorenz H, Schmidt H, Sipos B, Pawlak M, Gierke B, Kreider R, Lankat-Buttgereit B, Sauer M, Fiedler L, et al: PLAC8 localizes to the inner plasma membrane of pancreatic cancer cells and regulates cell growth and disease progression through critical cell-cycle regulatory pathways. Cancer Res. 76:96–107. 2016. View Article : Google Scholar : PubMed/NCBI
10	Uehara H, Takahashi T and Izumi K: Induction of retinol-binding protein 4 and placenta-specific 8 expression in human prostate cancer cells remaining in bone following osteolytic tumor growth inhibition by osteoprotegerin. Int J Oncol. 43:365–374. 2013. View Article : Google Scholar : PubMed/NCBI
11	Zou L, Chai J, Gao Y, Guan J, Liu Q and Du JJ: Down-regulated PLAC8 promotes hepatocellular carcinoma cell proliferation by enhancing PI3K/Akt/GSK3β/Wnt/β-catenin signaling. Biomed Pharmacother. 84:139–146. 2016. View Article : Google Scholar : PubMed/NCBI
12	Li C, Ma H, Wang Y, Cao Z, Graves-Deal R, Powell AE, Starchenko A, Ayers GD, Washington MK, Kamath V, et al: Excess PLAC8 promotes an unconventional ERK2-dependent EMT in colon cancer. J Clin Invest. 124:2172–2187. 2014. View Article : Google Scholar : PubMed/NCBI
13	Shi L, Xiao L, Heng B, Mo S, Chen W and Su Z: Overexpression of placenta specific 8 is associated with malignant progression and poor prognosis of clear cell renal cell carcinoma. Int Urol Nephrol. 49:1165–1176. 2017. View Article : Google Scholar : PubMed/NCBI
14	Xu X, Chai S, Wang P, Zhang C, Yang Y, Yang Y and Wang K: Aldehyde dehydrogenases and cancer stem cells. Cancer Lett. 369:50–57. 2015. View Article : Google Scholar : PubMed/NCBI
15	Koppaka V, Thompson DC, Chen Y, Ellermann M, Nicolaou KC, Juvonen RO, Petersen D, Deitrich RA, Hurley TD and Vasiliou V: Aldehyde dehydrogenase inhibitors: a comprehensive review of the pharmacology, mechanism of action, substrate specificity, and clinical application. Pharmacol Rev. 64:520–539. 2012. View Article : Google Scholar : PubMed/NCBI
16	Yu J, Alharbi A, Shan H, Hao Y, Snetsinger B, Rauh MJ and Yang X: TAZ induces lung cancer stem cell properties and tumorigenesis by up-regulating ALDH1A1. Oncotarget. 8:38426–38443. 2017.PubMed/NCBI
17	Duong HQ, You KS, Oh S, Kwak SJ and Seong YS: Silencing of NRF2 reduces the expression of ALDH1A1 and ALDH3A1 and sensitizes to 5-FU in pancreatic cancer cells. Antioxidants (Basel). 6(pii): E522017. View Article : Google Scholar : PubMed/NCBI
18	Alamgeer M, Ganju V, Szczepny A, Russell PA, Prodanovic Z, Kumar B, Wainer Z, Brown T, Schneider-Kolsky M, Conron M, et al: The prognostic significance of aldehyde dehydrogenase 1A1 (ALDH1A1) and CD133 expression in early stage non-small cell lung cancer. Thorax. 68:1095–1104. 2013. View Article : Google Scholar : PubMed/NCBI
19	Wei Y, Wu S, Xu W, Liang Y, Li Y, Zhao W and Wu J: Depleted aldehyde dehydrogenase 1A1 (ALDH1A1) reverses cisplatin resistance of human lung adenocarcinoma cell A549/DDP. Thorac Cancer. 8:26–32. 2017. View Article : Google Scholar : PubMed/NCBI
20	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
21	Lai YH, Lin SY, Wu YS, Chen HW and Chen JJW: AC-93253 iodide, a novel Src inhibitor, suppresses NSCLC progression by modulating multiple Src-related signaling pathways. J Hematol Oncol. 10:1722017. View Article : Google Scholar : PubMed/NCBI
22	Tan CS, Gilligan D and Pacey S: Treatment approaches for EGFR-inhibitor-resistant patients with non-small-cell lung cancer. Lancet Oncol. 16:e447–e459. 2015. View Article : Google Scholar : PubMed/NCBI
23	Yu HA, Arcila ME, Rekhtman N, Sima CS, Zakowski MF, Pao W, Kris MG, Miller VA, Ladanyi M and Riely GJ: Analysis of tumor specimens at the time of acquired resistance to EGFR-TKI therapy in 155 patients with EGFR-mutant lung cancers. Clin Cancer Res. 19:2240–2247. 2013. View Article : Google Scholar : PubMed/NCBI
24	Kolluru V, Pal D, Papu John AMS, Ankem MK, Freedman JH and Damodaran C: Induction of Plac8 promotes pro-survival function of autophagy in cadmium-induced prostate carcinogenesis. Cancer Lett. 408:121–129. 2017. View Article : Google Scholar : PubMed/NCBI
25	Kinsey C, Balakrishnan V, O'Dell MR, Huang JL, Newman L, Whitney-Miller CL, Hezel AF and Land H: Plac8 links oncogenic mutations to regulation of autophagy and is critical to pancreatic cancer progression. Cell Rep. 7:1143–1155. 2014. View Article : Google Scholar : PubMed/NCBI
26	Hanahan D and Weinberg RA: Hallmarks of cancer: The next generation. Cell. 144:646–674. 2011. View Article : Google Scholar : PubMed/NCBI
27	Leon G, MacDonagh L, Finn SP, Cuffe S and Barr MP: Cancer stem cells in drug resistant lung cancer: Targeting cell surface markers and signaling pathways. Pharmacol Ther. 158:71–90. 2016. View Article : Google Scholar : PubMed/NCBI
28	Prieto-Vila M, Takahashi RU, Usuba W, Kohama I and Ochiya T: Drug resistance driven by cancer stem cells and their niche. Int J Mol Sci. 18(pii): E25742017. View Article : Google Scholar : PubMed/NCBI
29	MacDonagh L, Gray SG, Breen E, Cuffe S, Finn SP, O'Byrne KJ and Barr MP: Lung cancer stem cells: The root of resistance. Cancer Lett. 372:147–156. 2016. View Article : Google Scholar : PubMed/NCBI
30	Hashida S, Yamamoto H, Shien K, Miyoshi Y, Ohtsuka T, Suzawa K, Watanabe M, Maki Y, Soh J, Asano H, et al: Acquisition of cancer stem cell-like properties in non-small cell lung cancer with acquired resistance to afatinib. Cancer Sci. 106:1377–1384. 2015. View Article : Google Scholar : PubMed/NCBI
31	Jimenez-Preitner M, Berney X and Thorens B: Plac8 is required for white adipocyte differentiation in vitro and cell number control in vivo. PLoS One. 7:e487672012. View Article : Google Scholar : PubMed/NCBI