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Published in: Cancer Cell International 1/2017

Open Access 01-12-2017 | Primary Research

Regulatory effects of COL1A1 on apoptosis induced by radiation in cervical cancer cells

Authors: Shurong Liu, Gewang Liao, Guowen Li

Published in: Cancer Cell International | Issue 1/2017

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Abstract

Background

Cervical cancer is a common cancer of women in developing countries, and radiotherapy still remains its predominant therapeutic treatment. Collagen type I alpha 1 (COL1A1) has been shown to have a radioresistance effect in previous studies. However, such effect of COL1A1 has not yet been revealed in cervical cancer.

Methods

Expression of COL1A1 in cervical cancer tissues and normal tissues was assessed by qRT-PCR and immunohistochemistry. The effect of COL1A1 on radioresistance of human cervical cancer cell lines HeLa and CaSki was assessed using the colony formation assay. Apoptosis alterations were analyzed by flow cytometry. In addition, western blotting was used assessed the alterations of several critical apoptosis and signaling pathway related proteins.

Results

The expression of COL1A1 was significantly increased in cervical cancer tissues compared with normal tissues at the mRNA and protein level. Further, based on COL1A1 knock down and COL1A1 activation cell models, a negative correlation was observed between COL1A1 expression level and radiosensitivity. Moreover, the findings are further supported by apoptosis analysis that COL1A1 activation could inhibit the apoptosis of cervical cancer cells. Subsequently, a significantly decreased expression of p-AKT and Bcl-2, increased expression of Caspase-3 were observed in the LY294002 plus radiation group compared with radiation alone group, while these influences caused by LY294002 or X-ray radiation were reversed after COL1A1 activation.

Conclusions

To our knowledge, this is the only study to profile the mechanisms that COL1A1 plays a crucial role in cervical cells anti-apoptosis induced by radiation. Therefore, our identification of radioresistance-related COL1A1 in cervical cancer could be a starting point to explore the function of collagens, adding a new dimension to our understanding of the cervical cancer, assisting cancer biologists and clinical oncologists in novel therapeutic strategies.
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Literature
1.
go back to reference Bermudez A, Bhatla N, Leung E. Cancer of the cervix uteri. Int J Gynaecol Obstet. 2015;131(Suppl 2):S88–95.CrossRefPubMed Bermudez A, Bhatla N, Leung E. Cancer of the cervix uteri. Int J Gynaecol Obstet. 2015;131(Suppl 2):S88–95.CrossRefPubMed
2.
go back to reference Fu JH, Gao Z, Ren CC, Shi YG. Comparison of clinical efficacy of three different neoadjuvant approaches (chemotherapy combined vaginal intracavitary irradiation, neoadjuvant chemotherapy alone or radiotherapy) combined with surgery for patients with stage Ib2 and IIa2 cervical cancer. Asian Pac J Cancer Prev. 2013;14(4):2377–81.CrossRefPubMed Fu JH, Gao Z, Ren CC, Shi YG. Comparison of clinical efficacy of three different neoadjuvant approaches (chemotherapy combined vaginal intracavitary irradiation, neoadjuvant chemotherapy alone or radiotherapy) combined with surgery for patients with stage Ib2 and IIa2 cervical cancer. Asian Pac J Cancer Prev. 2013;14(4):2377–81.CrossRefPubMed
3.
go back to reference Song L, Liu S, Zhang L, Yao H, Gao F, Xu D, Li Q. MiR-21 modulates radiosensitivity of cervical cancer through inhibiting autophagy via the PTEN/Akt/HIF-1alpha feedback loop and the Akt-mTOR signaling pathway. Tumour Biol. 2016;37(9):1–8.CrossRef Song L, Liu S, Zhang L, Yao H, Gao F, Xu D, Li Q. MiR-21 modulates radiosensitivity of cervical cancer through inhibiting autophagy via the PTEN/Akt/HIF-1alpha feedback loop and the Akt-mTOR signaling pathway. Tumour Biol. 2016;37(9):1–8.CrossRef
4.
go back to reference Herd O, Francies F, Kotzen J, Smith T, Nxumalo Z, Muller X, Slabbert J, Vral A, Baeyens A. Chromosomal radiosensitivity of human immunodeficiency virus positive/negative cervical cancer patients in South Africa. Mol Med Rep. 2016;13(1):130–6.PubMed Herd O, Francies F, Kotzen J, Smith T, Nxumalo Z, Muller X, Slabbert J, Vral A, Baeyens A. Chromosomal radiosensitivity of human immunodeficiency virus positive/negative cervical cancer patients in South Africa. Mol Med Rep. 2016;13(1):130–6.PubMed
5.
go back to reference Liu SS, Leung RC, Chan KY, Chiu PM, Cheung AN, Tam KF, Ng TY, Wong LC, Ngan HY. p73 expression is associated with the cellular radiosensitivity in cervical cancer after radiotherapy. Clin Cancer Res. 2004;10(10):3309–16.CrossRefPubMed Liu SS, Leung RC, Chan KY, Chiu PM, Cheung AN, Tam KF, Ng TY, Wong LC, Ngan HY. p73 expression is associated with the cellular radiosensitivity in cervical cancer after radiotherapy. Clin Cancer Res. 2004;10(10):3309–16.CrossRefPubMed
6.
go back to reference Belfatto A, Riboldi M, Ciardo D, Cattani F, Cecconi A, Lazzari R, Jereczek-Fossa BA, Orecchia R, Baroni G, Cerveri P. Kinetic models for predicting cervical cancer response to radiation therapy on individual basis using tumor regression measured in vivo with volumetric imaging. Technol Cancer Res Treat. 2016;15(1):146–58.CrossRefPubMed Belfatto A, Riboldi M, Ciardo D, Cattani F, Cecconi A, Lazzari R, Jereczek-Fossa BA, Orecchia R, Baroni G, Cerveri P. Kinetic models for predicting cervical cancer response to radiation therapy on individual basis using tumor regression measured in vivo with volumetric imaging. Technol Cancer Res Treat. 2016;15(1):146–58.CrossRefPubMed
7.
go back to reference Chan TF, Poon A, Basu A, Addleman NR, Chen J, Phong A, Byers PH, Klein TE, Kwok PY. Natural variation in four human collagen genes across an ethnically diverse population. Genomics. 2008;91(4):307–14.CrossRefPubMedPubMedCentral Chan TF, Poon A, Basu A, Addleman NR, Chen J, Phong A, Byers PH, Klein TE, Kwok PY. Natural variation in four human collagen genes across an ethnically diverse population. Genomics. 2008;91(4):307–14.CrossRefPubMedPubMedCentral
8.
go back to reference Zhao YP, Wang H, Fang M, Ji Q, Yang ZX, Gao CF. Study of the association between polymorphisms of the COL1A1 gene and HBV-related liver cirrhosis in Chinese patients. Dig Dis Sci. 2009;54(2):369–76.CrossRefPubMed Zhao YP, Wang H, Fang M, Ji Q, Yang ZX, Gao CF. Study of the association between polymorphisms of the COL1A1 gene and HBV-related liver cirrhosis in Chinese patients. Dig Dis Sci. 2009;54(2):369–76.CrossRefPubMed
9.
go back to reference Marini JC, Forlino A, Cabral WA, Barnes AM, San Antonio JD, Milgrom S, Hyland JC, Korkko J, Prockop DJ, De Paepe A, et al. Consortium for osteogenesis imperfecta mutations in the helical domain of type I collagen: regions rich in lethal mutations align with collagen binding sites for integrins and proteoglycans. Hum Mutat. 2007;28(3):209–21.CrossRefPubMedPubMedCentral Marini JC, Forlino A, Cabral WA, Barnes AM, San Antonio JD, Milgrom S, Hyland JC, Korkko J, Prockop DJ, De Paepe A, et al. Consortium for osteogenesis imperfecta mutations in the helical domain of type I collagen: regions rich in lethal mutations align with collagen binding sites for integrins and proteoglycans. Hum Mutat. 2007;28(3):209–21.CrossRefPubMedPubMedCentral
10.
go back to reference Carbone L, Harris RA, Gnerre S, Veeramah KR, Lorente-Galdos B, Huddleston J, Meyer TJ, Herrero J, Roos C, Aken B, et al. Gibbon genome and the fast karyotype evolution of small apes. Nature. 2014;513(7517):195–201.CrossRefPubMedPubMedCentral Carbone L, Harris RA, Gnerre S, Veeramah KR, Lorente-Galdos B, Huddleston J, Meyer TJ, Herrero J, Roos C, Aken B, et al. Gibbon genome and the fast karyotype evolution of small apes. Nature. 2014;513(7517):195–201.CrossRefPubMedPubMedCentral
11.
go back to reference Li AQ, Si JM, Shang Y, Gan LH, Guo L, Zhou TH. Construction of COL1A1 short hairpin RNA vector and its effect on cell proliferation and migration of gastric cancer cells. Zhejiang da xue xue bao Yi xue ban. 2010;39(3):257–63.PubMed Li AQ, Si JM, Shang Y, Gan LH, Guo L, Zhou TH. Construction of COL1A1 short hairpin RNA vector and its effect on cell proliferation and migration of gastric cancer cells. Zhejiang da xue xue bao Yi xue ban. 2010;39(3):257–63.PubMed
12.
go back to reference Sun H. Identification of key genes associated with gastric cancer based on DNA microarray data. Oncol Lett. 2016;11(1):525–30.PubMed Sun H. Identification of key genes associated with gastric cancer based on DNA microarray data. Oncol Lett. 2016;11(1):525–30.PubMed
13.
go back to reference Kitahara O, Katagiri T, Tsunoda T, Harima Y, Nakamura Y. Classification of sensitivity or resistance of cervical cancers to ionizing radiation according to expression profiles of 62 genes selected by cDNA microarray analysis. Neoplasia. 2002;4(4):295–303.CrossRefPubMedPubMedCentral Kitahara O, Katagiri T, Tsunoda T, Harima Y, Nakamura Y. Classification of sensitivity or resistance of cervical cancers to ionizing radiation according to expression profiles of 62 genes selected by cDNA microarray analysis. Neoplasia. 2002;4(4):295–303.CrossRefPubMedPubMedCentral
14.
go back to reference Cruet-Hennequart S, Drougard C, Shaw G, Legendre F, Demoor M, Barry F, Lefaix JL, Galera P. Radiation-induced alterations of osteogenic and chondrogenic differentiation of human mesenchymal stem cells. PLoS ONE. 2015;10(3):e0119334.CrossRefPubMedPubMedCentral Cruet-Hennequart S, Drougard C, Shaw G, Legendre F, Demoor M, Barry F, Lefaix JL, Galera P. Radiation-induced alterations of osteogenic and chondrogenic differentiation of human mesenchymal stem cells. PLoS ONE. 2015;10(3):e0119334.CrossRefPubMedPubMedCentral
15.
go back to reference Hayashi M, Nomoto S, Hishida M, Inokawa Y, Kanda M, Okamura Y, Nishikawa Y, Tanaka C, Kobayashi D, Yamada S, et al. Identification of the collagen type 1 alpha 1 gene (COL1A1) as a candidate survival-related factor associated with hepatocellular carcinoma. BMC Cancer. 2014;14:108.CrossRefPubMedPubMedCentral Hayashi M, Nomoto S, Hishida M, Inokawa Y, Kanda M, Okamura Y, Nishikawa Y, Tanaka C, Kobayashi D, Yamada S, et al. Identification of the collagen type 1 alpha 1 gene (COL1A1) as a candidate survival-related factor associated with hepatocellular carcinoma. BMC Cancer. 2014;14:108.CrossRefPubMedPubMedCentral
16.
go back to reference Quinn MC, Wojnarowicz PM, Pickett A, Provencher DM, Mes-Masson AM, Davis EC, Tonin PN. FKBP10/FKBP65 expression in high-grade ovarian serous carcinoma and its association with patient outcome. Int J Oncol. 2013;42(3):912–20.PubMed Quinn MC, Wojnarowicz PM, Pickett A, Provencher DM, Mes-Masson AM, Davis EC, Tonin PN. FKBP10/FKBP65 expression in high-grade ovarian serous carcinoma and its association with patient outcome. Int J Oncol. 2013;42(3):912–20.PubMed
17.
go back to reference Zhang Q, Gao M, Luo G, Han X, Bao W, Cheng Y, Tian W, Yan M, Yang G, An J. Enhancement of radiation sensitivity in lung cancer cells by a novel small molecule inhibitor that targets the beta-catenin/Tcf4 interaction. PLoS ONE. 2016;11(3):e0152407.CrossRefPubMedPubMedCentral Zhang Q, Gao M, Luo G, Han X, Bao W, Cheng Y, Tian W, Yan M, Yang G, An J. Enhancement of radiation sensitivity in lung cancer cells by a novel small molecule inhibitor that targets the beta-catenin/Tcf4 interaction. PLoS ONE. 2016;11(3):e0152407.CrossRefPubMedPubMedCentral
18.
go back to reference Bose MV, Rajkumar T. Assessment of the radiation sensitivity of cervical cancer cell lines. Methods Mol Biol. 2015;1249:351–62.CrossRefPubMed Bose MV, Rajkumar T. Assessment of the radiation sensitivity of cervical cancer cell lines. Methods Mol Biol. 2015;1249:351–62.CrossRefPubMed
19.
go back to reference da Seong B, Hong S, Muthusami S, Kim WD, Yu JR, Park WY. Cordycepin increases radiosensitivity in cervical cancer cells by overriding or prolonging radiation-induced G2/M arrest. Eur J Pharmacol. 2016;771:77–83.CrossRef da Seong B, Hong S, Muthusami S, Kim WD, Yu JR, Park WY. Cordycepin increases radiosensitivity in cervical cancer cells by overriding or prolonging radiation-induced G2/M arrest. Eur J Pharmacol. 2016;771:77–83.CrossRef
20.
go back to reference Lagadic-Gossmann D, Huc L, Lecureur V. Alterations of intracellular pH homeostasis in apoptosis: origins and roles. Cell Death Differ. 2004;11(9):953–61.CrossRefPubMed Lagadic-Gossmann D, Huc L, Lecureur V. Alterations of intracellular pH homeostasis in apoptosis: origins and roles. Cell Death Differ. 2004;11(9):953–61.CrossRefPubMed
21.
go back to reference Tsujimoto Y, Finger LR, Yunis J, Nowell PC, Croce CM. Cloning of the chromosome breakpoint of neoplastic B cells with the t(14;18) chromosome translocation. Science. 1984;226(4678):1097–9.CrossRefPubMed Tsujimoto Y, Finger LR, Yunis J, Nowell PC, Croce CM. Cloning of the chromosome breakpoint of neoplastic B cells with the t(14;18) chromosome translocation. Science. 1984;226(4678):1097–9.CrossRefPubMed
22.
go back to reference Cleary ML, Smith SD, Sklar J. Cloning and structural analysis of cDNAs for bcl-2 and a hybrid bcl-2/immunoglobulin transcript resulting from the t(14;18) translocation. Cell. 1986;47(1):19–28.CrossRefPubMed Cleary ML, Smith SD, Sklar J. Cloning and structural analysis of cDNAs for bcl-2 and a hybrid bcl-2/immunoglobulin transcript resulting from the t(14;18) translocation. Cell. 1986;47(1):19–28.CrossRefPubMed
23.
go back to reference Westphal D, Kluck RM, Dewson G. Building blocks of the apoptotic pore: how Bax and Bak are activated and oligomerize during apoptosis. Cell Death Differ. 2014;21(2):196–205.CrossRefPubMed Westphal D, Kluck RM, Dewson G. Building blocks of the apoptotic pore: how Bax and Bak are activated and oligomerize during apoptosis. Cell Death Differ. 2014;21(2):196–205.CrossRefPubMed
25.
go back to reference Li X, Zhang Q, Cai L, Wang Y, Wang Q, Huang X, Fu S, Bai J, Liu J, Zhang G, et al. Inhibitor of growth 4 induces apoptosis in human lung adenocarcinoma cell line A549 via Bcl-2 family proteins and mitochondria apoptosis pathway. J Cancer Res Clin Oncol. 2009;135(6):829–35.CrossRefPubMed Li X, Zhang Q, Cai L, Wang Y, Wang Q, Huang X, Fu S, Bai J, Liu J, Zhang G, et al. Inhibitor of growth 4 induces apoptosis in human lung adenocarcinoma cell line A549 via Bcl-2 family proteins and mitochondria apoptosis pathway. J Cancer Res Clin Oncol. 2009;135(6):829–35.CrossRefPubMed
26.
go back to reference Mace PD, Riedl SJ, Salvesen GS. Caspase enzymology and activation mechanisms. Methods Enzymol. 2014;544:161–78.CrossRefPubMed Mace PD, Riedl SJ, Salvesen GS. Caspase enzymology and activation mechanisms. Methods Enzymol. 2014;544:161–78.CrossRefPubMed
27.
go back to reference Liu J, Eischeid AN, Chen XM. Col1A1 production and apoptotic resistance in TGF-β1-induced epithelial-to-mesenchymal transition-like phenotype of 603B cells. PLoS ONE. 2012;7(12):e51371.CrossRefPubMedPubMedCentral Liu J, Eischeid AN, Chen XM. Col1A1 production and apoptotic resistance in TGF-β1-induced epithelial-to-mesenchymal transition-like phenotype of 603B cells. PLoS ONE. 2012;7(12):e51371.CrossRefPubMedPubMedCentral
28.
go back to reference Hosper NA, van den Berg PP, de Rond S, Popa ER, Wilmer MJ, Masereeuw R, Bank RA. Epithelial-to-mesenchymal transition in fibrosis: collagen type I expression is highly upregulated after EMT, but does not contribute to collagen deposition. Exp Cell Res. 2013;319(19):3000–9.CrossRefPubMed Hosper NA, van den Berg PP, de Rond S, Popa ER, Wilmer MJ, Masereeuw R, Bank RA. Epithelial-to-mesenchymal transition in fibrosis: collagen type I expression is highly upregulated after EMT, but does not contribute to collagen deposition. Exp Cell Res. 2013;319(19):3000–9.CrossRefPubMed
29.
go back to reference Halim TA, Farooqi AA, Zaman F. Nip the HPV encoded evil in the cancer bud: HPV reshapes TRAILs and signaling landscapes. Cancer Cell Int. 2013;13(1):61.CrossRefPubMedPubMedCentral Halim TA, Farooqi AA, Zaman F. Nip the HPV encoded evil in the cancer bud: HPV reshapes TRAILs and signaling landscapes. Cancer Cell Int. 2013;13(1):61.CrossRefPubMedPubMedCentral
30.
go back to reference Theys J, Jutten B, Habets R, Paesmans K, Groot AJ, Lambin P, Wouters BG, Lammering G, Vooijs M. E-cadherin loss associated with EMT promotes radioresistance in human tumor cells. Radiother Oncol. 2011;99(3):392–7.CrossRefPubMedPubMedCentral Theys J, Jutten B, Habets R, Paesmans K, Groot AJ, Lambin P, Wouters BG, Lammering G, Vooijs M. E-cadherin loss associated with EMT promotes radioresistance in human tumor cells. Radiother Oncol. 2011;99(3):392–7.CrossRefPubMedPubMedCentral
31.
go back to reference Marieegyptienne DT, Lohse I, Hill RP. Cancer stem cells, the epithelial to mesenchymal transition (EMT) and radioresistance: potential role of hypoxia. Cancer Lett. 2013;341(1):63–72.CrossRef Marieegyptienne DT, Lohse I, Hill RP. Cancer stem cells, the epithelial to mesenchymal transition (EMT) and radioresistance: potential role of hypoxia. Cancer Lett. 2013;341(1):63–72.CrossRef
32.
go back to reference Liu X, Li Z, Song Y, Wang R, Han L, Wang Q, Jiang K, Kang C, Zhang Q. AURKA induces EMT by regulating histone modification through Wnt/β-catenin and PI3K/Akt signaling pathway in gastric cancer. Oncotarget. 2016;7(22):33152–64.CrossRefPubMedPubMedCentral Liu X, Li Z, Song Y, Wang R, Han L, Wang Q, Jiang K, Kang C, Zhang Q. AURKA induces EMT by regulating histone modification through Wnt/β-catenin and PI3K/Akt signaling pathway in gastric cancer. Oncotarget. 2016;7(22):33152–64.CrossRefPubMedPubMedCentral
33.
go back to reference Lee YJ, Han HJ. Troglitazone ameliorates high glucose-induced EMT and dysfunction of SGLTs through PI3K/Akt, GSK-3β, Snail1, and β-catenin in renal proximal tubule cells. Am J Physiol Renal Physiol. 2010;298(5):F1263.CrossRefPubMed Lee YJ, Han HJ. Troglitazone ameliorates high glucose-induced EMT and dysfunction of SGLTs through PI3K/Akt, GSK-3β, Snail1, and β-catenin in renal proximal tubule cells. Am J Physiol Renal Physiol. 2010;298(5):F1263.CrossRefPubMed
34.
go back to reference Ni J, Cozzi P, Hao J, Beretov J, Chang L, Duan W, Shigdar S, Delprado W, Graham P, Bucci J. Epithelial cell adhesion molecule (EpCAM) is associated with prostate cancer metastasis and chemo/radioresistance via the PI3K/Akt/mTOR signaling pathway. Int J Biochem Cell Biol. 2013;45(12):2736–48.CrossRefPubMed Ni J, Cozzi P, Hao J, Beretov J, Chang L, Duan W, Shigdar S, Delprado W, Graham P, Bucci J. Epithelial cell adhesion molecule (EpCAM) is associated with prostate cancer metastasis and chemo/radioresistance via the PI3K/Akt/mTOR signaling pathway. Int J Biochem Cell Biol. 2013;45(12):2736–48.CrossRefPubMed
35.
go back to reference Silva MF, Khokhar AR, Qureshi MZ, Farooqi AA. Ionizing radiations induce apoptosis in TRAIL resistant cancer cells: in vivo and in vitro analysis. Asian Pac J Cancer Prev. 2014;15(5):1905–7.CrossRefPubMed Silva MF, Khokhar AR, Qureshi MZ, Farooqi AA. Ionizing radiations induce apoptosis in TRAIL resistant cancer cells: in vivo and in vitro analysis. Asian Pac J Cancer Prev. 2014;15(5):1905–7.CrossRefPubMed
Metadata
Title
Regulatory effects of COL1A1 on apoptosis induced by radiation in cervical cancer cells
Authors
Shurong Liu
Gewang Liao
Guowen Li
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2017
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/s12935-017-0443-5

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