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http://dx.doi.org/10.14348/molcells.2018.0311

OCT4B Isoform Promotes Anchorage-Independent Growth of Glioblastoma Cells  

Choi, Sang-Hun (Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University)
Kim, Jun-Kyum (Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University)
Jeon, Hee-Young (Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University)
Eun, Kiyoung (Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University)
Kim, Hyunggee (Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University)
Publication Information
Molecules and Cells / v.42, no.2, 2019 , pp. 135-142 More about this Journal
Abstract
OCT4, also known as POU5F1 (POU domain class 5 transcription factor 1), is a transcription factor that acts as a master regulator of pluripotency in embryonic stem cells and is one of the reprogramming factors required for generating induced pluripotent stem cells. The human OCT4 encodes three isoforms, OCT4A, OCT4B, and OCT4B1, which are generated by alternative splicing. Currently, the functions and expression patterns of OCT4B remain largely unknown in malignancies, especially in human glioblastomas. Here, we demonstrated the function of OCT4B in human glioblastomas. Among the isoform of OCT4B, OCT4B-190 ($OCT4B^{19kDa}$) was highly expressed in human glioblastoma stem cells and glioblastoma cells and was mainly detected in the cytoplasm rather than the nucleus. Overexpression of $OCT4B^{19kDa}$ promoted colony formation of glioblastoma cells when grown in soft agar culture conditions. Clinical data analysis revealed that patients with gliomas that expressed OCT4B at high levels had a poorer prognosis than patients with gliomas that expressed OCT4B at low levels. Thus, $OCT4B^{19kDa}$ may play a crucial role in regulating cancer cell survival and adaption in a rigid environment.
Keywords
anchorage-independent growth; cytoplasmic localization; glioblastoma; mechanical stress response; OCT4B;
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1 Mao, P., Joshi, K., Li, J., Kim, S.H., Li, P., Santana-Santos, L., Luthra, S., Chandran, U.R., Benos, P.V., Smith, L., et al. (2013). Mesenchymal glioma stem cells are maintained by activated glycolytic metabolism involving aldehyde dehydrogenase 1A3. Proc. Natl. Acad. Sci. USA 110, 8644-8649.   DOI
2 Pickup, M.W., Mouw, J.K., and Weaver, V.M. (2014). The extracellular matrix modulates the hallmarks of cancer. EMBO Rep. 15, 1243-1253.   DOI
3 Radzisheuskaya, A., and Silva, J.C. (2014). Do all roads lead to Oct4? the emerging concepts of induced pluripotency. Trends Cell Biol. 24, 275-284.   DOI
4 Rijlaarsdam, M.A., van Herk, H.A., Gillis, A.J., Stoop, H., Jenster, G., Martens, J., van Leenders, G.J., Dinjens, W., Hoogland, A.M., Timmermans, M., et al. (2011). Specific detection of OCT3/4 isoform A/B/B1 expression in solid (germ cell) tumours and cell lines: confirmation of OCT3/4 specificity for germ cell tumours. Br. J. Cancer 105, 854-863.   DOI
5 Subramanian, A., Tamayo, P., Mootha, V.K., Mukherjee, S., Ebert, B.L., Gillette, M.A., Paulovich, A., Pomeroy, S.L., Golub, T.R., Lander, E.S., et al. (2005). Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc. Natl. Acad. Sci. USA 102, 15545-15550.   DOI
6 Takahashi, K., and Yamanaka, S. (2006). Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126, 663-676.   DOI
7 Takeda, J., Seino, S., and Bell, G.I. (1992). Human Oct3 gene family: cDNA sequences, alternative splicing, gene organization, chromosomal location, and expression at low levels in adult tissues. Nucleic Acids Res. 20, 4613-4620.   DOI
8 Abiko, K., Mandai, M., Hamanishi, J., Matsumura, N., Baba, T., Horiuchi, A., Mikami, Y., Yoshioka, S., Wakasa, T., Shiozawa, T., et al. (2010). Oct4 expression in immature teratoma of the ovary: relevance to histologic grade and degree of differentiation. Am. J. Surg. Pathol. 34, 1842-1848.   DOI
9 Asadi, M.H., Mowla, S.J., Fathi, F., Aleyasin, A., Asadzadeh, J., and Atlasi, Y. (2011). OCT4B1, a novel spliced variant of OCT4, is highly expressed in gastric cancer and acts as an antiapoptotic factor. Int. J. Cancer 128, 2645-2652.   DOI
10 Asadzadeh, J., Asadi, M.H., Shakhssalim, N., Rafiee, M.R., Kalhor, H.R., Tavallaei, M., and Mowla, S.J. (2012). A plausible anti-apoptotic role of up-regulated OCT4B1 in bladder tumors. Urol. J. 9, 574-580.
11 Atlasi, Y., Mowla, S.J., Ziaee, S.A., Gokhale, P.J., and Andrews, P.W. (2008). OCT4 spliced variants are differentially expressed in human pluripotent and nonpluripotent cells. Stem Cells 26, 3068-3074.   DOI
12 Ben-Porath, I., Thomson, M.W., Carey, V.J., Ge, R., Bell, G.W., Regev, A., and Weinberg, R.A. (2008). An embryonic stem cell-like gene expression signature in poorly differentiated aggressive human tumors. Nat. Genet. 40, 499-507.   DOI
13 Bonnans, C., Chou, J., and Werb, Z. (2014). Remodelling the extracellular matrix in development and disease. Nat. Rev. Mol. Cell Biol. 15, 786-801.   DOI
14 Bronsert, P., Enderle-Ammour, K., Bader, M., Timme, S., Kuehs, M., Csanadi, A., Kayser, G., Kohler, I., Bausch, D., Hoeppner, J., et al. (2014). Cancer cell invasion and EMT marker expression: a threedimensional study of the human cancer-host interface. J. Pathol. 234, 410-422.   DOI
15 Butcher, D.T., Alliston, T., and Weaver, V.M. (2009). A tense situation: forcing tumour progression. Nat. Rev. Cancer 9, 108-122.   DOI
16 Du, Z., Jia, D., Liu, S., Wang, F., Li, G., Zhang, Y., Cao, X., Ling, E.A., and Hao, A. (2009). Oct4 is expressed in human gliomas and promotes colony formation in glioma cells. Glia 57, 724-733.   DOI
17 Eun, K., Ham, S.W., and Kim, H. (2017). Cancer stem cell heterogeneity: origin and new perspectives on CSC targeting. BMB Rep. 50, 117-125.   DOI
18 Gao, Y., Wang, X., Han, J., Xiao, Z., Chen, B., Su, G., and Dai, J. (2010). The novel OCT4 spliced variant OCT4B1 can generate three protein isoforms by alternative splicing into OCT4B. J. Genet. Genomics 37, 461-465.   DOI
19 Gao, Y., Wei, J., Han, J., Wang, X., Su, G., Zhao, Y., Chen, B., Xiao, Z., Cao, J., and Dai, J. (2012). The novel function of OCT4B isoform-265 in genotoxic stress. Stem. Cells 30, 665-672.   DOI
20 Gazouli, M., Roubelakis, M.G., Theodoropoulos, G.E., Papailiou, J., Vaiopoulou, A., Pappa, K.I., Nikiteas, N., and Anagnou, N.P. (2012). OCT4 spliced variant OCT4B1 is expressed in human colorectal cancer. Mol. Carcinog. 51, 165-173.   DOI
21 Verhaak, R.G., Hoadley, K.A., Purdom, E., Wang, V., Qi, Y., Wilkerson, M.D., Miller, C.R., Ding, L., Golub, T., Mesirov, J.P., et al. (2010). Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1. Cancer Cell 17, 98-110.   DOI
22 Vogel, V. (2018). Unraveling the mechanobiology of extracellular matrix. Annu. Rev. Physiol. 80, 353-387.   DOI
23 Wang, X., and Dai, J. (2010). Concise review: isoforms of OCT4 contribute to the confusing diversity in stem cell biology. Stem. Cells 28, 885-893.
24 Wang, X., Zhao, Y., Xiao, Z., Chen, B., Wei, Z., Wang, B., Zhang, J., Han, J., Gao, Y., Li, L., et al. (2009). Alternative translation of OCT4 by an internal ribosome entry site and its novel function in stress response. Stem. Cells 27, 1265-1275.   DOI
25 Han, S.W., and Roman, J. (2006). Fibronectin induces cell proliferation and inhibits apoptosis in human bronchial epithelial cells: pro-oncogenic effects mediated by PI3-kinase and NF-kappa B. Oncogene 25, 4341-4349.   DOI
26 Kim, J.K., Jeon, H.Y., and Kim, H. (2015). The molecular mechanisms underlying the therapeutic resistance of cancer stem cells. Arch. Pharm. Res. 38, 389-401.   DOI
27 Yu, Q., Xue, Y., Liu, J., Xi, Z., Li, Z., and Liu, Y. (2018). Fibronectin promotes the malignancy of glioma stem-like cells via modulation of cell adhesion, differentiation, proliferation and chemoresistance. Front. Mol. Neurosci. 11, 130.   DOI
28 Koo, B.S., Lee, S.H., Kim, J.M., Huang, S., Kim, S.H., Rho, Y.S., Bae, W.J., Kang, H.J., Kim, Y.S., Moon, J.H., et al. (2015). Oct4 is a critical regulator of stemness in head and neck squamous carcinoma cells. Oncogene 34, 2317-2324.   DOI
29 Kumar, S.M., Liu, S., Lu, H., Zhang, H., Zhang, P.J., Gimotty, P.A., Guerra, M., Guo, W., Xu, X., et al. (2012). Acquired cancer stem cell phenotypes through Oct4-mediated dedifferentiation. Oncogene 31, 4898-4911.   DOI
30 Lathia, J.D., Mack, S.C., Mulkearns-Hubert, E.E., Valentim, C.L., and Rich, J.N. (2015). Cancer stem cells in glioblastoma. Genes Dev. 29, 1203-1217.   DOI
31 Lee, J., Kim, H.K., Rho, J.Y., Han, Y.M., and Kim, J. (2006). The human OCT-4 isoforms differ in their ability to confer self-renewal. J. Biol. Chem. 281, 33554-33565.   DOI
32 Li, S.W., Wu, X.L., Dong, C.L., Xie, X.Y., Wu, J.F., and Zhang, X. (2015). The differential expression of OCT4 isoforms in cervical carcinoma. PLoS One 10, e0118033.   DOI
33 Mammoto, T., Jiang, E., Jiang, A., and Mammoto, A. (2013). Extracellular matrix structure and tissue stiffness control postnatal lung development through the lipoprotein receptor-related protein 5/Tie2 signaling system. Am. J. Respir. Cell Mol. Biol. 49, 1009-1018.   DOI