Placenta-specific protein 1 promotes cell proliferation and invasion in non-small cell lung cancer

Yang,Li; Zha,Tian-Qi; He,Xiang; Chen,Liang; Zhu,Quan; Wu,Wei-Bing; Nie,Feng-Qi; Wang,Qian; Zang,Chong-Shuang; Zhang,Mei-Ling; He,Jing; Li,Wei; Jiang,Wen; Lu,Kai-Hua

doi:10.3892/or.2017.6086

Placenta-specific protein 1 promotes cell proliferation and invasion in non-small cell lung cancer

Authors:
- Li Yang
- Tian-Qi Zha
- Xiang He
- Liang Chen
- Quan Zhu
- Wei-Bing Wu
- Feng-Qi Nie
- Qian Wang
- Chong-Shuang Zang
- Mei-Ling Zhang
- Jing He
- Wei Li
- Wen Jiang
- Kai-Hua Lu
View Affiliations

Affiliations: Department of Oncology, First Affiliated Hospital, Nanjing Medical University, Gulou, Nanjing, Jiangsu 210029, P.R. China, Department of Digestive, First Affiliated Hospital, Nanjing Medical University, Gulou, Nanjing, Jiangsu 210029, P.R. China, Department of Cardiothoracic Surgery, First Affiliated Hospital, Nanjing Medical University, Gulou, Nanjing, Jiangsu 210029, P.R. China, Department of Oncology, Second Affiliated Hospital, Nanjing Medical University, Gulou, Nanjing, Jiangsu 210029, P.R. China, Department of Biochemistry, Nanjing Medical University, Gulou, Nanjing, Jiangsu 210029, P.R. China
Published online on: November 9, 2017 https://doi.org/10.3892/or.2017.6086
Pages: 53-60
Copyright: © Yang 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

Pulmonary carcinoma-associated proteins have emerged as crucial players in governing fundamental biological processes such as cell proliferation, apoptosis and metastasis in human cancers. Placenta-specific protein 1 (PLAC1) is a cancer-related protein, which is activated and upregulated in a variety of malignant tissues, including prostate cancer, gastric adenocarcinoma, colorectal, epithelial ovarian and breast cancer. However, its biological role and clinical significance in non-small cell lung cancer (NSCLC) development and progression are still unknown. In the present study, we found that PLAC1 was significantly upregulated in NSCLC tissues, and its expression level was associated with advanced pathological stage and it was also correlated with shorter progression-free survival of lung cancer patients. Furthermore, knockdown of PLAC1 expression by siRNA inhibited cell proliferation, induced apoptosis and impaired invasive ability in NSCLC cells partly via regulation of epithelial-mesenchymal transition (EMT)-related protein expression. Our findings present that increased PLAC1 could be identified as a negative prognostic biomarker in NSCLC and regulate cell proliferation and invasion. Thus, we conclusively demonstrated that PLAC1 plays a key role in NSCLC development and progression, which may provide novel insights on the function of tumor-related gene-driven tumorigenesis.

View Figures

View References

1	Siegel RL, Miller KD and Jemal A: Cancer statistics, 2015. CA Cancer J Clin. 65:5–29. 2015. View Article : Google Scholar : PubMed/NCBI
2	Travis WD, Brambilla E, Nicholson AG, Yatabe Y, Austin JH, Beasley MB, Chirieac LR, Dacic S, Duhig E, Flieder DB, et al: WHO Panel: The 2015 World Health Organization Classification of Lung Tumors: Impact of Genetic, Clinical and Radiologic Advances Since the 2004 Classification. J Thorac Oncol. 10:1243–1260. 2015. View Article : Google Scholar : PubMed/NCBI
3	Herbst RS, Heymach JV and Lippman SM: Lung cancer. N Engl J Med. 359:1367–1380. 2008. View Article : Google Scholar : PubMed/NCBI
4	Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, Jemal A, Yu XQ and He J: Cancer statistics in China, 2015. CA Cancer J Clin. 66:115–132. 2016. View Article : Google Scholar : PubMed/NCBI
5	Jung KW, Park S, Kong HJ, Won YJ, Lee JY, Seo HG and Lee JS: Cancer statistics in Korea: Incidence, mortality, survival, and prevalence in 2009. Cancer Res Treat. 44:1–24. 2012. View Article : Google Scholar : PubMed/NCBI
6	Chaari A, Ben Nasr S, Labidi S, Afrit M and Boussen H: Metastatic non-small cell lung cancer: A Tunisian retrospective study about 100 cases. Tunis Med. 93:294–296. 2015.(In French). PubMed/NCBI
7	Geiger TR and Peeper DS: Metastasis mechanisms. Biochim Biophys Acta. 1796:293–308. 2009.PubMed/NCBI
8	Chan DA and Giaccia AJ: Hypoxia, gene expression, and metastasis. Cancer Metastasis Rev. 26:333–339. 2007. View Article : Google Scholar : PubMed/NCBI
9	Headley MB, Bins A, Nip A, Roberts EW, Looney MR, Gerard A and Krummel MF: Visualization of immediate immune responses to pioneer metastatic cells in the lung. Nature. 531:513–517. 2016. View Article : Google Scholar : PubMed/NCBI
10	Rankin EB and Giaccia AJ: Hypoxic control of metastasis. Science. 352:175–180. 2016. View Article : Google Scholar : PubMed/NCBI
11	Turajlic S and Swanton C: Metastasis as an evolutionary process. Science. 352:169–175. 2016. View Article : Google Scholar : PubMed/NCBI
12	Cheung KJ and Ewald AJ: A collective route to metastasis: Seeding by tumor cell clusters. Science. 352:167–169. 2016. View Article : Google Scholar : PubMed/NCBI
13	Kiberstis PA: Metastasis: An evolving story. Science. 352:162–163. 2016. View Article : Google Scholar : PubMed/NCBI
14	Tüting T and de Visser KE: CANCER. How neutrophils promote metastasis. Science. 352:145–146. 2016. View Article : Google Scholar : PubMed/NCBI
15	Swanton C and Govindan R: Clinical implications of genomic discoveries in lung cancer. N Engl J Med. 374:1864–1873. 2016. View Article : Google Scholar : PubMed/NCBI
16	Wang X, Baddoo MC and Yin Q: The placental specific gene, PLAC1, is induced by the Epstein-Barr virus and is expressed in human tumor cells. Virol J. 11:1072014. View Article : Google Scholar : PubMed/NCBI
17	Silva WA Jr, Gnjatic S, Ritter E, Chua R, Cohen T, Hsu M, Jungbluth AA, Altorki NK, Chen YT, Old LJ, et al: PLAC1, a trophoblast-specific cell surface protein, is expressed in a range of human tumors and elicits spontaneous antibody responses. Cancer Immun. 7:182007.PubMed/NCBI
18	Fant M, Barerra-Saldana H, Dubinsky W, Poindexter B and Bick R: The PLAC1 protein localizes to membranous compartments in the apical region of the syncytiotrophoblast. Mol Reprod Dev. 74:922–929. 2007. View Article : Google Scholar : PubMed/NCBI
19	Massabbal E, Parveen S, Weisoly DL, Nelson DM, Smith SD and Fant M: PLAC1 expression increases during trophoblast differentiation: Evidence for regulatory interactions with the fibroblast growth factor-7 (FGF-7) axis. Mol Reprod Dev. 71:299–304. 2005. View Article : Google Scholar : PubMed/NCBI
20	Rawn SM and Cross JC: The evolution, regulation, and function of placenta-specific genes. Annu Rev Cell Dev Biol. 24:159–181. 2008. View Article : Google Scholar : PubMed/NCBI
21	Fant M, Weisoly DL, Cocchia M, Huber R, Khan S, Lunt T and Schlessinger D: PLAC1, a trophoblast-specific gene, is expressed throughout pregnancy in the human placenta and modulated by keratinocyte growth factor. Mol Reprod Dev. 63:430–436. 2002. View Article : Google Scholar : PubMed/NCBI
22	Chang WL, Yang Q, Zhang H, Lin HY, Zhou Z, Lu X, Zhu C, Xue LQ and Wang H: Role of placenta-specific protein 1 in trophoblast invasion and migration. Reproduction. 148:343–352. 2014. View Article : Google Scholar : PubMed/NCBI
23	Dong XY, Peng JR, Ye YJ, Chen HS, Zhang LJ, Pang XW, Li Y, Zhang Y, Wang S, Fant ME, et al: Plac1 is a tumor-specific antigen capable of eliciting spontaneous antibody responses in human cancer patients. Int J Cancer. 122:2038–2043. 2008. View Article : Google Scholar : PubMed/NCBI
24	Liu F, Shen D, Kang X, Zhang C and Song Q: New tumour antigen PLAC1/CP1, a potentially useful prognostic marker and immunotherapy target for gastric adenocarcinoma. J Clin Pathol. 68:913–916. 2015. View Article : Google Scholar : PubMed/NCBI
25	Liu F, Zhang H, Shen D, Wang S, Ye Y, Chen H, Pang X, Song Q and He P: Identification of two new HLA-A*0201-restricted cytotoxic T lymphocyte epitopes from colorectal carcinoma-associated antigen PLAC1/CP1. J Gastroenterol. 49:419–426. 2014. View Article : Google Scholar : PubMed/NCBI
26	Liu FF, Shen DH, Wang S, Ye YJ and Song QJ: Expression of PLAC1/CP1 genes in primary colorectal carcinoma and its clinical significance. Zhonghua Bing Li Xue Za Zhi. 39:810–813. 2010.(In Chinese). PubMed/NCBI
27	Ghods R, Ghahremani MH, Madjd Z, Asgari M, Abolhasani M, Tavasoli S, Mahmoudi AR, Darzi M, Pasalar P, Jeddi-Tehrani M, et al: High placenta-specific 1/low prostate-specific antigen expression pattern in high-grade prostate adenocarcinoma. Cancer Immunol Immunother. 63:1319–1327. 2014. View Article : Google Scholar : PubMed/NCBI
28	Liu W, Zhai M, Wu Z, Qi Y, Wu Y, Dai C, Sun M, Li L and Gao Y: Identification of a novel HLA-A2-restricted cytotoxic T lymphocyte epitope from cancer-testis antigen PLAC1 in breast cancer. Amino Acids. 42:2257–2265. 2012. View Article : Google Scholar : PubMed/NCBI
29	Tchabo NE, Mhawech-Fauceglia P, Caballero OL, Villella J, Beck AF, Miliotto AJ, Liao J, Andrews C, Lele S, Old LJ, et al: Expression and serum immunoreactivity of developmentally restricted differentiation antigens in epithelial ovarian cancer. Cancer Immun. 9:62009.PubMed/NCBI
30	Koslowski M, Türeci O, Biesterfeld S, Seitz G, Huber C and Sahin U: Selective activation of trophoblast-specific PLAC1 in breast cancer by CCAAT/enhancer-binding protein beta (C/EBPbeta) isoform 2. J Biol Chem. 284:28607–28615. 2009. View Article : Google Scholar : PubMed/NCBI
31	Koslowski M, Sahin U, Mitnacht-Kraus R, Seitz G, Huber C and Türeci O: A placenta-specific gene ectopically activated in many human cancers is essentially involved in malignant cell processes. Cancer Res. 67:9528–9534. 2007. View Article : Google Scholar : PubMed/NCBI
32	Cantley LC: The phosphoinositide 3-kinase pathway. Science. 296:1655–1657. 2002. View Article : Google Scholar : PubMed/NCBI
33	Luo J, Manning BD and Cantley LC: Targeting the PI3K-Akt pathway in human cancer: Rationale and promise. Cancer Cell. 4:257–262. 2003. View Article : Google Scholar : PubMed/NCBI
34	Yeh PS, Wang W, Chang YA, Lin CJ, Wang JJ and Chen RM: Honokiol induces autophagy of neuroblastoma cells through activating the PI3K/Akt/mTOR and endoplasmic reticular stress/ERK1/2 signaling pathways and suppressing cell migration. Cancer Lett. 370:66–77. 2016. View Article : Google Scholar : PubMed/NCBI
35	Chen X, Guan X, Zhang H, Xie X, Wang H, Long J, Cai T, Li S, Liu Z and Zhang Y: DAL-1 attenuates epithelial-to mesenchymal transition in lung cancer. J Exp Clin Cancer Res. 34:32015. View Article : Google Scholar : PubMed/NCBI
36	Mittal V: Epithelial mesenchymal transition in aggressive lung cancers. Adv Exp Med Biol. 890:37–56. 2016. View Article : Google Scholar : PubMed/NCBI
37	Pattabiraman DR, Bierie B, Kober KI, Thiru P, Krall JA, Zill C, Reinhardt F, Tam WL and Weinberg RA: Activation of PKA leads to mesenchymal-to-epithelial transition and loss of tumor-initiating ability. Science. 351:aad36802016. View Article : Google Scholar : PubMed/NCBI
38	Seton-Rogers S: Epithelial-mesenchymal transition: Untangling EMT's functions. Nat Rev Cancer. 16:12016. View Article : Google Scholar : PubMed/NCBI
39	Cocchia M, Huber R, Pantano S, Chen EY, Ma P, Forabosco A, Ko MS and Schlessinger D: PLAC1, an Xq26 gene with placenta-specific expression. Genomics. 68:305–312. 2000. View Article : Google Scholar : PubMed/NCBI
40	Fant M, Farina A, Nagaraja R and Schlessinger D: PLAC1 (Placenta-specific 1): A novel, X-linked gene with roles in reproductive and cancer biology. Prenat Diagn. 30:497–502. 2010.PubMed/NCBI