Skip to main content
Top
Published in: Tumor Biology 5/2016

01-05-2016 | Original Article

Upregulation of PTEN suppresses invasion in Tca8113 tongue cancer cells through repression of epithelial–mesenchymal transition (EMT)

Authors: Siming Xie, Zhiyuan Lu, Yanzhu Lin, Lijia Shen, Cao Yin

Published in: Tumor Biology | Issue 5/2016

Login to get access

Abstract

We previously discovered that the expression of the tumor suppressor phosphatase and tensin homolog (PTEN) was downregulated in the majority patients with tongue squamous cell carcinoma (TSCC). The aim of this study was to investigate the role of PTEN overexpression in the regulation of epithelial–mesenchymal transition (EMT) of the tongue squamous carcinoma cell line Tca8113 as well as explore the underlying mechanism. GV230 (containing the PTEN gene) and empty vectors were transfected into Tca8113 cells. After stable transfection, the messenger RNA (mRNA) and protein levels of PTEN were validated using quantitative real-time PCR (qPCR) and Western blot analysis. The growth and cell cycle were analyzed using Cell Counting Kit-8 (CCK-8) and flow cytometry, respectively. The invasion ability was measured with a transwell assay. The effects of PTEN overexpression on EMT and Hedgehog signaling were assessed by comparing Tca8113-PTEN cells with control and negative control cell groups. We found that PTEN expression was significantly upregulated after transfection. Meanwhile, upregulated PTEN inhibited the proliferation and invasion of Tca8113 cells. In addition, we observed changes in the EMT- and Hedgehog-associated proteins. These data demonstrated that PTEN upregulation could reduce invasion by inhibiting the process of EMT in Tca8113 cells, which might be related to the Hedgehog signaling pathway.
Literature
1.
go back to reference Mao L, Hong WK, Papadimitrakopoulou VA. Focus on head and neck cancer. Cancer Cell. 2004;5:311–6.CrossRefPubMed Mao L, Hong WK, Papadimitrakopoulou VA. Focus on head and neck cancer. Cancer Cell. 2004;5:311–6.CrossRefPubMed
2.
go back to reference Davis SJ, Divi V, Owen JH, Bradford CR, Carey TE, Papagerakis S, et al. Metastatic potential of cancer stem cells in head and neck squamous cell carcinoma. Arch Otolaryngol Head Neck Surg. 2010;136:1260–6.CrossRefPubMedPubMedCentral Davis SJ, Divi V, Owen JH, Bradford CR, Carey TE, Papagerakis S, et al. Metastatic potential of cancer stem cells in head and neck squamous cell carcinoma. Arch Otolaryngol Head Neck Surg. 2010;136:1260–6.CrossRefPubMedPubMedCentral
3.
go back to reference Song MS, Salmena L, Pandolfi PP. The functions and regulation of the PTEN tumour suppressor. Nat Rev Mol Cell Biol. 2012;13:283–96.PubMed Song MS, Salmena L, Pandolfi PP. The functions and regulation of the PTEN tumour suppressor. Nat Rev Mol Cell Biol. 2012;13:283–96.PubMed
4.
go back to reference Chu EC, Tarnawski AS. PTEN regulatory functions in tumor suppression and cell biology. Med Sci Monit. 2004;10:RA235–41.PubMed Chu EC, Tarnawski AS. PTEN regulatory functions in tumor suppression and cell biology. Med Sci Monit. 2004;10:RA235–41.PubMed
5.
go back to reference Colakoglu T, Yildirim S, Kayaselcuk F, Nursal TZ, Ezer A, Noyan T, et al. Clinicopathological significance of pten loss and the phosphoinositide 3-kinase/Akt pathway in sporadic colorectal neoplasms: Is PTEN loss predictor of local recurrence? Am J Surg. 2008;195:719–25.CrossRefPubMed Colakoglu T, Yildirim S, Kayaselcuk F, Nursal TZ, Ezer A, Noyan T, et al. Clinicopathological significance of pten loss and the phosphoinositide 3-kinase/Akt pathway in sporadic colorectal neoplasms: Is PTEN loss predictor of local recurrence? Am J Surg. 2008;195:719–25.CrossRefPubMed
6.
go back to reference Rychahou PG, Kang J, Gulhati P, Doan HQ, Chen LA, Xiao SY, et al. Akt2 overexpression plays a critical role in the establishment of colorectal cancer metastasis. Proc Natl Acad Sci U S A. 2008;105:20315–20.CrossRefPubMedPubMedCentral Rychahou PG, Kang J, Gulhati P, Doan HQ, Chen LA, Xiao SY, et al. Akt2 overexpression plays a critical role in the establishment of colorectal cancer metastasis. Proc Natl Acad Sci U S A. 2008;105:20315–20.CrossRefPubMedPubMedCentral
7.
go back to reference Yao SXLSCYPRX. Expression of tumor suppressor gene PTEN, PIP3 and cyclin D1 in oral squamous cell carcinoma and their correlation. Chin J Stomatol. 2006;41:407–10. Yao SXLSCYPRX. Expression of tumor suppressor gene PTEN, PIP3 and cyclin D1 in oral squamous cell carcinoma and their correlation. Chin J Stomatol. 2006;41:407–10.
8.
go back to reference Shen CYRHHJZLSXYGL. Expression and the correlation of PTEN and CXCR4 protein in oral squamous cell carcinoma and precancerous lesions. J Dent Prev Treat. 2015;23:61–5. Shen CYRHHJZLSXYGL. Expression and the correlation of PTEN and CXCR4 protein in oral squamous cell carcinoma and precancerous lesions. J Dent Prev Treat. 2015;23:61–5.
9.
go back to reference Thompson EW, Newgreen DF, Tarin D. Carcinoma invasion and metastasis: a role for epithelial-mesenchymal transition? Cancer Res. 2005;65:5991–5. discussion 5995.CrossRefPubMed Thompson EW, Newgreen DF, Tarin D. Carcinoma invasion and metastasis: a role for epithelial-mesenchymal transition? Cancer Res. 2005;65:5991–5. discussion 5995.CrossRefPubMed
10.
go back to reference Zhou BB, Zhang H, Damelin M, Geles KG, Grindley JC, Dirks PB. Tumour-initiating cells: challenges and opportunities for anticancer drug discovery. Nat Rev Drug Discov. 2009;8:806–23.CrossRefPubMed Zhou BB, Zhang H, Damelin M, Geles KG, Grindley JC, Dirks PB. Tumour-initiating cells: challenges and opportunities for anticancer drug discovery. Nat Rev Drug Discov. 2009;8:806–23.CrossRefPubMed
11.
go back to reference Huber MA, Kraut N, Beug H. Molecular requirements for epithelial-mesenchymal transition during tumor progression. Curr Opin Cell Biol. 2005;17:548–58.CrossRefPubMed Huber MA, Kraut N, Beug H. Molecular requirements for epithelial-mesenchymal transition during tumor progression. Curr Opin Cell Biol. 2005;17:548–58.CrossRefPubMed
12.
go back to reference Garg M. Epithelial-mesenchymal transition—activating transcription factors—multifunctional regulators in cancer. World J Stem Cells. 2013;5:188–95.CrossRefPubMedPubMedCentral Garg M. Epithelial-mesenchymal transition—activating transcription factors—multifunctional regulators in cancer. World J Stem Cells. 2013;5:188–95.CrossRefPubMedPubMedCentral
14.
go back to reference Kokkinos MI, Wafai R, Wong MK, Newgreen DF, Thompson EW, Waltham M. Vimentin and epithelial-mesenchymal transition in human breast cancer—observations in vitro and in vivo. Cells Tissues Organs. 2007;185:191–203.CrossRefPubMed Kokkinos MI, Wafai R, Wong MK, Newgreen DF, Thompson EW, Waltham M. Vimentin and epithelial-mesenchymal transition in human breast cancer—observations in vitro and in vivo. Cells Tissues Organs. 2007;185:191–203.CrossRefPubMed
15.
go back to reference Hazelbag S, Kenter GG, Gorter A, Fleuren GJ. Prognostic relevance of TGF-beta1 and PAI-1 in cervical cancer. Int J Cancer. 2004;112:1020–8.CrossRefPubMed Hazelbag S, Kenter GG, Gorter A, Fleuren GJ. Prognostic relevance of TGF-beta1 and PAI-1 in cervical cancer. Int J Cancer. 2004;112:1020–8.CrossRefPubMed
16.
go back to reference Lastowska M, Al-Afghani H, Al-Balool HH, Sheth H, Mercer E, Coxhead JM, et al. Identification of a neuronal transcription factor network involved in medulloblastoma development. Acta Neuropathol Commun. 2013;1:35.CrossRefPubMedPubMedCentral Lastowska M, Al-Afghani H, Al-Balool HH, Sheth H, Mercer E, Coxhead JM, et al. Identification of a neuronal transcription factor network involved in medulloblastoma development. Acta Neuropathol Commun. 2013;1:35.CrossRefPubMedPubMedCentral
17.
go back to reference Haque I, De A, Majumder M, Mehta S, McGregor D, Banerjee SK, et al. The matricellular protein CCN1/Cyr61 is a critical regulator of sonic hedgehog in pancreatic carcinogenesis. J Biol Chem. 2012;287:38569–79.CrossRefPubMedPubMedCentral Haque I, De A, Majumder M, Mehta S, McGregor D, Banerjee SK, et al. The matricellular protein CCN1/Cyr61 is a critical regulator of sonic hedgehog in pancreatic carcinogenesis. J Biol Chem. 2012;287:38569–79.CrossRefPubMedPubMedCentral
18.
go back to reference Lu JT, Zhao WD, He W, Wei W. Hedgehog signaling pathway mediates invasion and metastasis of hepatocellular carcinoma via ERK pathway. Acta Pharmacol Sin. 2012;33:691–700.CrossRefPubMedPubMedCentral Lu JT, Zhao WD, He W, Wei W. Hedgehog signaling pathway mediates invasion and metastasis of hepatocellular carcinoma via ERK pathway. Acta Pharmacol Sin. 2012;33:691–700.CrossRefPubMedPubMedCentral
19.
go back to reference Flemban A, Qualtrough D. The potential role of hedgehog signaling in the luminal/basal phenotype of breast epithelia and in breast cancer invasion and metastasis. Cancers. 2015;7:1863–84.CrossRefPubMedPubMedCentral Flemban A, Qualtrough D. The potential role of hedgehog signaling in the luminal/basal phenotype of breast epithelia and in breast cancer invasion and metastasis. Cancers. 2015;7:1863–84.CrossRefPubMedPubMedCentral
21.
go back to reference Li X, Lin G, Wu B, Zhou X, Zhou K. Overexpression of PTEN induces cell growth arrest and apoptosis in human breast cancer ZR-75-1 cells. Acta Biochim Biophys Sin. 2007;39:745–50.CrossRefPubMed Li X, Lin G, Wu B, Zhou X, Zhou K. Overexpression of PTEN induces cell growth arrest and apoptosis in human breast cancer ZR-75-1 cells. Acta Biochim Biophys Sin. 2007;39:745–50.CrossRefPubMed
22.
go back to reference Yang L, Kuang LG, Zheng HC, Li JY, Wu DY, Zhang SM, et al. PTEN encoding product: a marker for tumorigenesis and progression of gastric carcinoma. World J Gastroenterol. 2003;9:35–9.CrossRefPubMedPubMedCentral Yang L, Kuang LG, Zheng HC, Li JY, Wu DY, Zhang SM, et al. PTEN encoding product: a marker for tumorigenesis and progression of gastric carcinoma. World J Gastroenterol. 2003;9:35–9.CrossRefPubMedPubMedCentral
23.
go back to reference Mulholland DJ, Kobayashi N, Ruscetti M, Zhi A, Tran LM, Huang J, et al. Pten loss and RAS/MAPK activation cooperate to promote EMT and metastasis initiated from prostate cancer stem/progenitor cells. Cancer Res. 2012;72:1878–89.CrossRefPubMedPubMedCentral Mulholland DJ, Kobayashi N, Ruscetti M, Zhi A, Tran LM, Huang J, et al. Pten loss and RAS/MAPK activation cooperate to promote EMT and metastasis initiated from prostate cancer stem/progenitor cells. Cancer Res. 2012;72:1878–89.CrossRefPubMedPubMedCentral
24.
go back to reference Bao L, Yan Y, Xu C, Ji W, Shen S, Xu G, et al. MicroRNA-21 suppresses pten and hSulf-1 expression and promotes hepatocellular carcinoma progression through AKT/ERK pathways. Cancer Lett. 2013;337:226–36.CrossRefPubMed Bao L, Yan Y, Xu C, Ji W, Shen S, Xu G, et al. MicroRNA-21 suppresses pten and hSulf-1 expression and promotes hepatocellular carcinoma progression through AKT/ERK pathways. Cancer Lett. 2013;337:226–36.CrossRefPubMed
25.
go back to reference Tanaka N, Odajima T, Ogi K, Ikeda T, Satoh M. Expression of e-cadherin, alpha-catenin, and beta-catenin in the process of lymph node metastasis in oral squamous cell carcinoma. Br J Cancer. 2003;89:557–63.CrossRefPubMedPubMedCentral Tanaka N, Odajima T, Ogi K, Ikeda T, Satoh M. Expression of e-cadherin, alpha-catenin, and beta-catenin in the process of lymph node metastasis in oral squamous cell carcinoma. Br J Cancer. 2003;89:557–63.CrossRefPubMedPubMedCentral
26.
go back to reference Thiery JP. Epithelial-mesenchymal transitions in tumour progression. Nat Rev Cancer. 2002;2:442–54.CrossRefPubMed Thiery JP. Epithelial-mesenchymal transitions in tumour progression. Nat Rev Cancer. 2002;2:442–54.CrossRefPubMed
27.
go back to reference Dahmane N, Lee J, Robins P, Heller P, Ruiz i Altaba A. Activation of the transcription factor Gli1 and the Sonic hedgehog signalling pathway in skin tumours. Nature. 1997;389:876–81.CrossRefPubMed Dahmane N, Lee J, Robins P, Heller P, Ruiz i Altaba A. Activation of the transcription factor Gli1 and the Sonic hedgehog signalling pathway in skin tumours. Nature. 1997;389:876–81.CrossRefPubMed
28.
go back to reference Berman DM, Karhadkar SS, Maitra A, Montes De Oca R, Gerstenblith MR, Briggs K, et al. Widespread requirement for hedgehog ligand stimulation in growth of digestive tract tumours. Nature. 2003;425:846–51.CrossRefPubMed Berman DM, Karhadkar SS, Maitra A, Montes De Oca R, Gerstenblith MR, Briggs K, et al. Widespread requirement for hedgehog ligand stimulation in growth of digestive tract tumours. Nature. 2003;425:846–51.CrossRefPubMed
29.
go back to reference de Oliveira SD, Loyola AM, Cardoso SV, Chammas R, Liu FT, de Faria PR. Hedgehog signaling pathway mediates tongue tumorigenesis in wild-type mice but not in Gal3-deficient mice. Exp Mol Pathol. 2014;97:332–7.CrossRef de Oliveira SD, Loyola AM, Cardoso SV, Chammas R, Liu FT, de Faria PR. Hedgehog signaling pathway mediates tongue tumorigenesis in wild-type mice but not in Gal3-deficient mice. Exp Mol Pathol. 2014;97:332–7.CrossRef
30.
go back to reference Metcalfe C, Alicke B, Crow A, Lamoureux M, Dijkgraaf GJ, Peale F, et al. PTEN loss mitigates the response of medulloblastoma to hedgehog pathway inhibition. Cancer Res. 2013;73:7034–42.CrossRefPubMed Metcalfe C, Alicke B, Crow A, Lamoureux M, Dijkgraaf GJ, Peale F, et al. PTEN loss mitigates the response of medulloblastoma to hedgehog pathway inhibition. Cancer Res. 2013;73:7034–42.CrossRefPubMed
31.
go back to reference Filbin MG, Dabral SK, Pazyra-Murphy MF, Ramkissoon S, Kung AL, Pak E, et al. Coordinate activation of Shh and PI3K signaling in pten-deficient glioblastoma: new therapeutic opportunities. Nat Med. 2013;19:1518–23.CrossRefPubMed Filbin MG, Dabral SK, Pazyra-Murphy MF, Ramkissoon S, Kung AL, Pak E, et al. Coordinate activation of Shh and PI3K signaling in pten-deficient glioblastoma: new therapeutic opportunities. Nat Med. 2013;19:1518–23.CrossRefPubMed
32.
go back to reference Inaguma S, Kasai K, Hashimoto M, Ikeda H. Gli1 modulates EMT in pancreatic cancer—letter. Cancer Res. 2012;72:3702–3. author reply 3704–3705.CrossRefPubMed Inaguma S, Kasai K, Hashimoto M, Ikeda H. Gli1 modulates EMT in pancreatic cancer—letter. Cancer Res. 2012;72:3702–3. author reply 3704–3705.CrossRefPubMed
Metadata
Title
Upregulation of PTEN suppresses invasion in Tca8113 tongue cancer cells through repression of epithelial–mesenchymal transition (EMT)
Authors
Siming Xie
Zhiyuan Lu
Yanzhu Lin
Lijia Shen
Cao Yin
Publication date
01-05-2016
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 5/2016
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-015-4486-8

Other articles of this Issue 5/2016

Tumor Biology 5/2016 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine