The invasion and metastasis are linked to the rapid progression and poor prognosis of hepatocarcinoma patients. Lymphatic metastasis is potentially involved in above pathogenesis with unclear mechanism. Previously, we found the deregulation of annexin A5 (ANXA5), a member of Ca2+-regulated phospholipid- and membrane-binding annexin family protein, mediated the in vivo malignancy, lymph node metastasis (LNM) rate and level of mice transplanted with Hca-P, a murine hepatocarcinoma cell line with the LNM potential rate of ~25%. Current work aimed to investigate the influence with action mechanism of ANXA5 overexpression on the in vitro malignant behaviours of Hca-P cells. For overexpressing ANXA5, the Anxa5 gene was ligated into pCDNA3.1 (+) vector and transfected into Hca-P named as Hca-P-ANXA5up. Hca-P transfected with empty pCDNA3.1 (+) vector was named as Hca-P-mock and used as the control. The monoclonal Hca-P-mock and Hca-P-ANXA5up cell lines were obtained against G418 screening using limiting dilution method. Compared with the Hca-P-mock cells, Western blotting assay indicated ANXA5 expression level was increased by 50.1% (p=0.025) in the Hca-P-ANXA5up cells. Transwell chamber assays indicated that the migration and invasion capacities of Hca-P-ANXA5up cells were increased by 150.2% (p=0.001) and 94.8% (p=0.003) than Hca-P-mock cells. ANXA5 overexpression enhanced the levels of p-MEK (Ser217/221), ERK1, ERK2, p-ERK1 (Thr202/Tyr204) and p-ERK2 (Thr185/Tyr187), and suppressed the levels of E-Cadherin, Snail and Slug in Hca-P cells. Current work shows ANXA5 overexpression enhances the malignant behaviours of hepatocarcinoma Hca-P cells through activating p-MEK-ERK pathway and suppressing E-Cadherin, Snail and Slug. It is of potential value in tumor malignancy and lymphatic metastasis of hepatocarcinoma.
| Published in | American Journal of Life Sciences (Volume 7, Issue 1) |
| DOI | 10.11648/j.ajls.20190701.16 |
| Page(s) | 31-37 |
| Creative Commons |
This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited. |
| Copyright |
Copyright © The Author(s), 2024. Published by Science Publishing Group |
Hepatocarcinoma, ANXA5, ERK, E-Cadherin
| [1] | W. Chen, R. Zheng, P. D. Baade, S. Zhang, H. Zeng, F. Bray, A. Jemal, X. Yu, and J. He, “Cancer statistics in China, 2015,” CA Cancer J. Clin. New York, 2016, vol. 66, pp. 115-132. |
| [2] | J. Zhang and Y. Qian, “Treatment options of postoperative recurrence of hepatocellular carcinoma,” Chin. J. Clinicians. Beijing, 2015, vol. 9, pp. 3319-3321. |
| [3] | Z. Tang, S. Ye, Y. Liu, L. Qin, H. Sun, Q. Ye, L. Wang, J. Zhou, S. Qiu, Y. Li, X. Ji, H. Liu, J. Xia, Z. Wu, J. Fan, Z. Ma, X. Zhou, Z. Lin, and K. Liu, “A decade’s studies on metastasis of hepatocellular carcinoma,” J. Cancer Res. Clin. Oncol. Berlin, 2004, vol. 130, pp. 187-196. |
| [4] | S. D. Nathanson, “Insights into the mechanisms of lymph node metastasis,” Cancer. New York, 2003, vol. 98, pp. 413-423. |
| [5] | S. Li and Q. Li, “Cancer stem cells, lymphangiogenesis, and lymphatic metastasis,” Cancer Letter. Amsterdam, 2014, vol. 357, pp. 438-447. |
| [6] | S. Stacker, M. Baldwin, and M. Achen, “The role of tumor lymphangiogenesis in metastatic spread,” FASEB J. Bethesda, 2002, vol. 16, pp. 922-934. |
| [7] | B. Peng, C. Guo, H. Guan, S. Liu, and M-Z. Sun, “Annexin A5 as a potential marker in tumors,” Clin. Chim. Acta. Amsterdam, 2014, vol. 427, pp. 42-48. |
| [8] | G. Xue, L. Hao, F. Ding, Q. Mei, J. Huang, C. Fu, H. Yan, and S. Sun, “Expression of annexin A5 is associated with higher tumor stage and poor prognosis in colorectal adenocarcinomas,” J. Clin. Gastroenterol. New York, 2009, vol. 43, pp. 831-837. |
| [9] | U. Rajcevic, K. Petersen, J. Knol, M. Loos, S. Bougnaud, O. Klychnikov, K. Li, T. Pham, J. Wang, H. Miletic, Z. Peng, R. Bjerkvig, C. Jimenez, and S. Niclou, “iTRAQ-based proteomics profiling feveals increased metabolic activity and cellular cross-talk in angiogenic compared with invasive glioblastoma phenotype,” Mol. Cell Proteomics. Bethesda, 2009, vol. 8, pp. 2595-2612. |
| [10] | M-Z. Sun, S. Liu, J. Tang, Z. Wang, X. Gong, C. Sun, and F. Greenaway, “Proteomics analysis of two mice hepatocarcinoma ascites syngeneic cell lines with high and low lymph node metastasis rates provide potential protein markers for tumor malignancy attributes to lymphatic metastasis,” Proteomics. Weinheim, 2009, vol. 9, pp. 3285-3302. |
| [11] | S. Liu, C. Guo, J. Wang, B. Wang, H. Qi, and M-Z. Sun, “ANXA11 regulates the tumorigenesis, lymph node metastasis and 5-fluorouracil sensitivity of murine hepatocarcinoma Hca-P cells by targeting c-Jun,” Oncotarget. Albany, 2016, vol. 7, pp. 16297-16310. |
| [12] | J. Shi, L. Meng, M-Z. Sun, C. Guo, X. Sun, Q. Lin, and S. Liu, “CRKL knockdown promotes in vitro proliferation, migration and invasion, in vivo tumor malignancy and lymph node metastasis of murine hepatocarcinoma Hca-P cells,” Biomed. Pharmacother. New York, 2015, vol. 71, pp. 84-90. |
| [13] | S. Liu, M-Z. Sun, J. Tang, Z. Wang, C. Sun, and F. T. Greenaway, “High-performance liquid chromatography/nano-electrospray ionization tandem mass spectrometry, two-dimensional difference in-gel electrophoresis and gene microarray identification of lymphatic metastasis-associated biomarkers,” Rapid Commun. Mass Spectrom. Chichester, 2008, vol. 22, pp. 3172-3178. |
| [14] | B. Peng, S. Liu, C. Guo, X. Sun, and M-Z. Sun, “Anxa5 level is linked to in vitro and in vivo tumor malignancy and lymphatic metastasis of murine hepatocarcinoma cell,” Future Oncol. London, 2016, vol. 12, pp. 31-42. |
| [15] | G. L. Johnson and R. Lapadat. “Mitogen-activated protein kinase pathways mediated by ERK, JNK, and p38 protein kinases,” Science. New York, 2002, vol. 298, pp. 1911-1912. |
| [16] | A. Mehdizadeh, M. H. Somi, M. Darabi, and M. Jabbarpour-Bonyadi, “Extracellular signal -regulated kinase 1 and 2 in cancer therapy: a focus on hepatocellular carcinoma,” Mol. Biol. Rep. Dordrecht, 2016, vol. 43, pp. 107-116. |
| [17] | H. Sato, H. Ogata, and L. M. De Luca, “Annexin V inhibits 12-O-tetradecanoylphorbol-13-acetate-induced activation of Ras/ extracellular signal-regulated kinase (ERK) signaling pathway upstream of Shc in MCF-7 cells,” Oncogene. Basingstoke, 2000, vol. 19, pp. 2904-2912. |
| [18] | M. A. Lizarbe, J. I. Barrasa, N. Olmo, F. Gavilanes, and J. Turnay, “Annexins-phospholipid interactions. Functional implications,” Int. J. Mol. Sci. Basel, 2013, vol. 14, pp. 2652-2683. |
| [19] | A. Laohavist and J. M. Davies, “Annexins,” New Phytol. London, 2011, vol. 189, pp. 40-53. |
| [20] | M-Z. Sun, S. Liu, and J. Tang. “Proteomics investigation of mouse hepatocarcinoma cell lines with different lymph node metastasis capacities,” Chem. J. Chin. Univ. Beijing, 2009, vol. 30, pp. 517-524. |
| [21] | H. Nakao, M. Watanabe, and M. Maki, “A new function of calphobind I (annexin V),” Eur. J. Biochem. Berlin, 1994, vol. 223, pp. 901-908. |
| [22] | X. Sun, B. Wei, S. Liu, C. Guo, N. Wu, Q. Liu, and M-Z. Sun, “Anxa5 mediates in vitro malignant behaviours of murine hepatocarcinoma Hca-F cells with high lymph node metastasis potential preferentially via ERK2/p-ERK2/c-Jun/p-c-Jun (Ser73) and E-cadherin,” Biomed Pharmacother. New York, 2016, vol. 84, pp. 645-654. |
| [23] | Q. Lin, M-Z. Sun, C. Guo, J. Shi, and X. Chen, “CRKL overexpression suppresses in vitro proliferation, invasion and migration of murine hepatocarcinoma Hca-P cells,” Biomed Pharmacother. New York, 2015, vol. 69, pp. 11-17. |
| [24] | J. Wu, J. Meng, Y. Du, Y. Huang, Y. Jin, J. Zhang, B. Wang, Y. Zhang, M-Z. Sun, and J. Tang, “RACK1 promotes the proliferation, migration and invasion capacity of mouse hepatocellular carcinoma cell line in vitro probably by PI3K/ Rac1 signaling pathway,” Biomed. Pharmacother. New York, 2013, vol. 67, pp. 313-319. |
| [25] | G. Guo, W. Yao, Q. Zhang, and Y. Bo, “Oleanolic acid suppresses migration and invasion of malignant glioma cells by inactivating MAPK/ERK signaling pathway,” PLoS One. San Francisco, 2013, vol. 8, pp. e72079. |
| [26] | P. Wang, Y. Zeng, T. Liu, C. Zhang, P. Yu, Y. Hao, H. Luo, and G. Liu, “Chloride intracellular channel 1 regulates colon cancer cell migration and invasion through ROS/ERK pathway,” World J. Gastroenterol. Beijing, 2014, vol. 20, pp. 2071-2078. |
| [27] | Y. Sun, W. Liu, T. Liu, X. Feng, N. Yang, and H. Zhou, “Signaling pathway of MAPK/ERK in cell proliferation, differentiation, migration, senescence and apoptosis,” J. Recept Signal Transduct Res. New York, 2015, vol. 35, pp. 600-604. |
| [28] | Y. Mebratu, and Y. Tesfaigzi, “How ERK1/2 activation controls cell proliferation and cell death is subcellular localization the answer?” Cell Cycle. Georgetown, 2009, vol. 8, pp. 1168- 1175. |
| [29] | M. Yilmaz, G. Christofori, and F. Lehembre, “Distinct mechanisms of tumor invasion and metastasis,” Trend Mol. Med. Oxford, 2007, vol. 13, pp. 535-541. |
| [30] | H. Semb and G. Christofori, “The tumor-suppressor function of E-cadherin,” Am. J. Hum. Genet. New York, 1998, vol. 63, pp. 1588-1593. |
| [31] | O. Schmalhofer, S. Brabletz, and T. Brabletz, “E-cadherin, β-catenin, and ZEB1 in malignant progression of cancer,” Cancer Met. Rev. The Hague, 2009, vol. 28 pp. 151-166. |
| [32] | M. R. Schneider and F. T. Kolligs, “E-cadherin’s role in development, tissue homeostasis and disease: Insights from mouse models tissue-specific inactivation of the adhesion protein E-cadherin in mice reveals its functions in health and disease,” Bioessays. Cambridge, 2015, vol. 37, pp. 294-304. |
| [33] | T. T. Onder, P. B. Gupta, and S. A. Mani, “Loss of E-Cadherin promotes metastasis via multiple downstream transcriptional pathways,” Cancer Res. Chicago, vol. 68, pp. 3645-3654. |
| [34] | E. Howard, K. Cam, Y. Wong, J. Yang, E. S. Lander, and R. A. Weinberg, “E-cadherin upregulation as a therapeutic goal in cancer treatment,” Mini. Rev. Med. Chem. Hilversum, 2008, vol. 8, pp. 496-518. |
| [35] | T. Chou, W. Chen, A. Lee, S. Hung, N. Shih, and M. Chen, “Clusterin silencing in human lung adenocarcinoma cells induces a mesenchymal-to-epithelial transition through modulating the ERK/Slug pathway,” Cell Signal. Oxford, 2009, vol. 21, pp. 704-711. |
| [36] | H. Peinado, F. Portillo, and A. Cano, “Transcriptional regulation of cadherins during development and carcinogenesis,” Int. J. Dev. Biol. Vizcaya, 2004, vol. 48, pp. 365-375. |
| [37] | T. Bhatt, A. Rizvi, S. Batta, S. Kataria, and C. Jamora, “Signaling and mechanical roles of E-cadherin,” Cell Commun. Adhes. Basingstoke, 2013, vol. 20, pp. 189-199. |
| [38] | A. Kudinov, A. Deneka, A. S. Nikonova, T. N. Beck, Y. Ahn, and X. Liu, “Musashi-2 (MSI2) supports TGF-β signaling and inhibits claudins to promote non-small cell lung cancer (NSCLC) metastasis,” Proc. Natl Acad. Sci. USA. Washington, 2016, vol. 113, pp. 6955 -6960. |
| [39] | K. Lu, G. Liu, L. Yang, F. Liu, L. Gao, J. Shi, X. Deng, Q. Li, D. Xu, and S. Shi, “Sustainable inflammation transforms hepatic cells by causing oxidative stress injury and potential epithelial-mesenchymal transition,” Int. J. Oncol. Athens, 2016, vol. 49, pp. 971-980. |
APA Style
Shuqing Liu, Chen Chen, Mingzhong Sun. (2019). ANXA5 Enhances Malignancy of Murine Hepatocarcinoma Hca-P Cells via ERK Activation and E-cadherin Suppression. American Journal of Life Sciences, 7(1), 31-37. https://doi.org/10.11648/j.ajls.20190701.16
ACS Style
Shuqing Liu; Chen Chen; Mingzhong Sun. ANXA5 Enhances Malignancy of Murine Hepatocarcinoma Hca-P Cells via ERK Activation and E-cadherin Suppression. Am. J. Life Sci. 2019, 7(1), 31-37. doi: 10.11648/j.ajls.20190701.16
AMA Style
Shuqing Liu, Chen Chen, Mingzhong Sun. ANXA5 Enhances Malignancy of Murine Hepatocarcinoma Hca-P Cells via ERK Activation and E-cadherin Suppression. Am J Life Sci. 2019;7(1):31-37. doi: 10.11648/j.ajls.20190701.16
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Download@article{10.11648/j.ajls.20190701.16,
author = {Shuqing Liu and Chen Chen and Mingzhong Sun},
title = {ANXA5 Enhances Malignancy of Murine Hepatocarcinoma Hca-P Cells via ERK Activation and E-cadherin Suppression},
journal = {American Journal of Life Sciences},
volume = {7},
number = {1},
pages = {31-37},
doi = {10.11648/j.ajls.20190701.16},
url = {https://doi.org/10.11648/j.ajls.20190701.16},
eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ajls.20190701.16},
abstract = {The invasion and metastasis are linked to the rapid progression and poor prognosis of hepatocarcinoma patients. Lymphatic metastasis is potentially involved in above pathogenesis with unclear mechanism. Previously, we found the deregulation of annexin A5 (ANXA5), a member of Ca2+-regulated phospholipid- and membrane-binding annexin family protein, mediated the in vivo malignancy, lymph node metastasis (LNM) rate and level of mice transplanted with Hca-P, a murine hepatocarcinoma cell line with the LNM potential rate of ~25%. Current work aimed to investigate the influence with action mechanism of ANXA5 overexpression on the in vitro malignant behaviours of Hca-P cells. For overexpressing ANXA5, the Anxa5 gene was ligated into pCDNA3.1 (+) vector and transfected into Hca-P named as Hca-P-ANXA5up. Hca-P transfected with empty pCDNA3.1 (+) vector was named as Hca-P-mock and used as the control. The monoclonal Hca-P-mock and Hca-P-ANXA5up cell lines were obtained against G418 screening using limiting dilution method. Compared with the Hca-P-mock cells, Western blotting assay indicated ANXA5 expression level was increased by 50.1% (p=0.025) in the Hca-P-ANXA5up cells. Transwell chamber assays indicated that the migration and invasion capacities of Hca-P-ANXA5up cells were increased by 150.2% (p=0.001) and 94.8% (p=0.003) than Hca-P-mock cells. ANXA5 overexpression enhanced the levels of p-MEK (Ser217/221), ERK1, ERK2, p-ERK1 (Thr202/Tyr204) and p-ERK2 (Thr185/Tyr187), and suppressed the levels of E-Cadherin, Snail and Slug in Hca-P cells. Current work shows ANXA5 overexpression enhances the malignant behaviours of hepatocarcinoma Hca-P cells through activating p-MEK-ERK pathway and suppressing E-Cadherin, Snail and Slug. It is of potential value in tumor malignancy and lymphatic metastasis of hepatocarcinoma.},
year = {2019}
}
TY - JOUR T1 - ANXA5 Enhances Malignancy of Murine Hepatocarcinoma Hca-P Cells via ERK Activation and E-cadherin Suppression AU - Shuqing Liu AU - Chen Chen AU - Mingzhong Sun Y1 - 2019/05/23 PY - 2019 N1 - https://doi.org/10.11648/j.ajls.20190701.16 DO - 10.11648/j.ajls.20190701.16 T2 - American Journal of Life Sciences JF - American Journal of Life Sciences JO - American Journal of Life Sciences SP - 31 EP - 37 PB - Science Publishing Group SN - 2328-5737 UR - https://doi.org/10.11648/j.ajls.20190701.16 AB - The invasion and metastasis are linked to the rapid progression and poor prognosis of hepatocarcinoma patients. Lymphatic metastasis is potentially involved in above pathogenesis with unclear mechanism. Previously, we found the deregulation of annexin A5 (ANXA5), a member of Ca2+-regulated phospholipid- and membrane-binding annexin family protein, mediated the in vivo malignancy, lymph node metastasis (LNM) rate and level of mice transplanted with Hca-P, a murine hepatocarcinoma cell line with the LNM potential rate of ~25%. Current work aimed to investigate the influence with action mechanism of ANXA5 overexpression on the in vitro malignant behaviours of Hca-P cells. For overexpressing ANXA5, the Anxa5 gene was ligated into pCDNA3.1 (+) vector and transfected into Hca-P named as Hca-P-ANXA5up. Hca-P transfected with empty pCDNA3.1 (+) vector was named as Hca-P-mock and used as the control. The monoclonal Hca-P-mock and Hca-P-ANXA5up cell lines were obtained against G418 screening using limiting dilution method. Compared with the Hca-P-mock cells, Western blotting assay indicated ANXA5 expression level was increased by 50.1% (p=0.025) in the Hca-P-ANXA5up cells. Transwell chamber assays indicated that the migration and invasion capacities of Hca-P-ANXA5up cells were increased by 150.2% (p=0.001) and 94.8% (p=0.003) than Hca-P-mock cells. ANXA5 overexpression enhanced the levels of p-MEK (Ser217/221), ERK1, ERK2, p-ERK1 (Thr202/Tyr204) and p-ERK2 (Thr185/Tyr187), and suppressed the levels of E-Cadherin, Snail and Slug in Hca-P cells. Current work shows ANXA5 overexpression enhances the malignant behaviours of hepatocarcinoma Hca-P cells through activating p-MEK-ERK pathway and suppressing E-Cadherin, Snail and Slug. It is of potential value in tumor malignancy and lymphatic metastasis of hepatocarcinoma. VL - 7 IS - 1 ER -
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