The role of osteopontin in the progression of solid organ tumour

Cell Death and Disease

Volumn 9, Issue 3, 2018, Pages

  Zhao, Hailin ^a   Chen, Qian ^a,b   Alam, Azeem ^a   Cui, Jiang ^a   Suen, Ka Chun ^a   Soo, Aurelie Pac ^a   Eguchi, Shiori ^a   Gu, Jianteng ^b   Ma, Daqing ^a  

^a CHELSEA AND WESTMINSTER HOSPITAL   (United Kingdom)

^b THIRD MILITARY MEDICAL UNIVERSITY   (China)

Author keywords

[No Author keywords available]

Indexed keywords

OSTEOPONTIN; TUMOR MARKER;

ANGIOGENESIS; BLADDER CANCER; BRAIN CANCER; BREAST CANCER; CANCER GROWTH; CANCER RESISTANCE; CARCINOGENESIS; CELL PROLIFERATION; COLORECTAL CANCER; ESOPHAGUS CANCER; HUMAN; KIDNEY CANCER; LIVER CANCER; LUNG CANCER; METASTASIS; MOLECULAR BIOLOGY; MOLECULAR PATHOLOGY; MOLECULARLY TARGETED THERAPY; NONHUMAN; OVARY CANCER; PANCREAS CANCER; PRIORITY JOURNAL; PROSTATE CANCER; PROTEIN FUNCTION; REVIEW; SOLID MALIGNANT NEOPLASM; STOMACH CANCER; TUMOR CELL; CELL ADHESION; CELL MOTION; DISEASE EXACERBATION; GENETICS; METABOLISM; NEOPLASM; NEOVASCULARIZATION (PATHOLOGY); PATHOLOGY;

BIOMARKERS, TUMOR; CELL ADHESION; CELL MOVEMENT; CELL PROLIFERATION; DISEASE PROGRESSION; HUMANS; MOLECULAR TARGETED THERAPY; NEOPLASM METASTASIS; NEOPLASMS; NEOVASCULARIZATION, PATHOLOGIC; OSTEOPONTIN;

EID: 85042791652     PISSN: None     EISSN: 20414889     Source Type: Journal    
DOI: 10.1038/s41419-018-0391-6     Document Type: Review

References (126)

1. Rangaswami, H., Bulbule, A. & Kundu, G. C. Osteopontin: role in cell signaling and cancer progression. Trends Cell. Biol. 16, 79-87 (2006).
2. Steinman L. A molecular trio in relapse and remission in multiple sclerosis. Nat Rev Immunol. 9, 440-7 (2009).
3. Yamamoto, N. et al. Essential role of the cryptic epitope SLAYGLR within osteopontin in a murine model of rheumatoid arthritis. J. Clin. Invest. 112, 181-188 (2003).
4. Sodek, J., Ganss, B. & McKee, M. D. Osteopontin. Crit. Rev. Oral. Biol. Med. 11, 279-303 (2000).
5. Senger, D. R., Perruzzi, C. A., Papadopoulos-Sergiou, A. & Van de Water, L. Adhesive properties of osteopontin: regulation by a naturally occurring thrombin-cleavage in close proximity to the GRGDS cell-binding domain. Mol. Biol. Cell. 5, 565-574 (1994).
6. Prochazka L, Tesarik R, Turanek J. Regulation of alternative splicing of CD44 in cancer. Cell Signal. 26, 2234-9 (2014).
7. Wang, K. X. & Denhardt, D. T. Osteopontin: role in immune regulation and stress responses. Cytokine Growth Factor. Rev. 19, 333-345 (2008).
8. Haylock, D. N. & Nilsson, S. K. Osteopontin: A bridge between bone and blood. Br. J. Haematol. 134, 467-474 (2006).
9. Reinholt, F. P., Hultenby, K., Oldberg, A. & Heinegard, D. Osteopontin-A possible anchor of osteoclasts to bone. Proc. Natl Acad. Sci. USA 87, 4473-4475 (1990).
10. Higashi, A. et al. The potential role of inflammation associated with interaction between osteopontin and CD44 in a case of pulmonary tumor thrombotic microangiopathy caused by breast cancer. Intern. Med. 54, 2877-2880 (2015).
11. Ramaiah, S. K. & Rittling, S. Pathophysiological role of osteopontin in hepatic inflammation, toxicity, and cancer. Toxicol. Sci. 103, 4-13 (2008).
12. Chen, Q. et al. Fate decision of mesenchymal stem cells: adipocytes or osteoblasts? Cell. Death. Differ. 23, 1128-1139 (2016).
13. Bellahcène A, Castronovo V, Ogbureke KU, Fisher LW, Fedarko NS. Small integrin-binding ligand N-linked glycoproteins (SIBLINGs): multifunctional proteins in cancer. Nat Rev Cancer. 8, 212-26 (2008)
14. Wai, P. Y. & Kuo, P. C. The role of osteopontin in tumor metastasis. J. Surg. Res. 121, 228-241 (2004).
15. Zhou, Y. et al. Osteopontin expression correlates with melanoma invasion. J. Invest. Dermatol. 124, 1044-1052 (2005).
16. Leali, D. et al. Osteopontin (Eta-1) and fibroblast growth factor-2 cross-talk in angiogenesis. J. Immunol. 171, 1085-1093 (2003).
17. Wirtz, D., Konstantopoulos, K. & Searson, P. C. The physics of cancer: the role of physical interactions and mechanical forces in metastasis. Nat. Rev. Cancer 11, 512-522 (2011).
18. Weber, G. F., Lett, G. S. & Haubein, N. C. Categorical meta-analysis of osteopontin as aclinical cancer marker. Oncol. Rep. 25, 433-441 (2011).
19. Kothari, A. N. et al. Osteopontin-A master regulator of epithelialmesenchymal transition. J. Clin. Med. 5, 1-16 (2016).
20. Li, N. Y. et al. Osteopontin up-regulates critical epithelial-mesenchymal transition transcription factors to induce an aggressive breast cancer phenotype. J. Am. Coll. Surg. 217, 17-26 (2013). discussion 26.
21. Dong, Q. et al. Osteopontin regulated epithelial-mesenchymal transition via PI3K/AKT signaling pathway in hepatocellular carcinoma. Cancer Res. 73, 2695-2695 (2013).
22. Ng, L. et al. Post-operative plasma osteopontin predicts distant metastasis in human colorectal cancer. PLoS. One. 10, e0126219 (2015).
23. Song, G. et al. Osteopontin promotes ovarian cancer progression and cell survival and increases HIF-1alpha expression through the PI3-K/Akt pathway. Cancer Sci. 99, 1901-1907 (2008).
24. Raja, R. et al. Hypoxia-driven osteopontin contributes to breast tumor growth through modulation of HIF1 alpha-mediated VEGF-dependent angiogenesis. Oncogene 33, 2053-2064 (2014).
25. Shevde, L. A. & Samant, R. S. Role of osteopontin in the pathophysiology of cancer. Matrix Biol. 37, 131-141 (2014).
26. Sui, X. et al. Autophagy and chemotherapy resistance: A promising therapeutic target for cancer treatment. Cell Death Dis. 4, e838 (2013).
27. Chang, S. H., Yu, K. N., Lee, K. A. & Cho, M. H. Autophagy execution protein beclin1 regulates radiation-induced osteopontin in human lung cancer cell. Lung. Cancer 77, S29-S29 (2012).
28. Yang, M. C. et al. Blockade of autophagy reduces pancreatic cancer stem cell activity and potentiates the tumoricidal effect of gemcitabine. Mol. Cancer 14, 179 (2015).
29. Liu, G. et al. Osteopontin induces autophagy to promote chemo-resistance in human hepatocellular carcinoma cells. Cancer Lett. 383, 171-182 (2016).
30. Yang, L. et al. Down-regulation of osteopontin expression by RNA interference affects cell proliferation and chemotherapy sensitivity of breast cancer MDA-MB-231 cells. Mol. Med. Rep. 5, 373-376 (2012).
31. Pang, H. et al. Knockdown of osteopontin chemosensitizes MDA-MB-231 cells to cyclophosphamide by enhancing apoptosis through activating p38 MAPK pathway. Cancer Biother Radio 26, 165-173 (2011).
32. Jan, H. J. et al. Osteopontin regulates human glioma cell invasiveness and tumor growth in mice. Neuro. Oncol. 12, 58-70 (2010).
33. Atai, N. A. et al. Osteopontin is up-regulated and associated with neutrophil and macrophage infiltration in glioblastoma. Immunology 132, 39-48 (2011).
34. Ding, Q. et al. Promotion of malignant astrocytoma cell migration by osteopontin expressed in the normal brain: differences in integrin signaling during cell adhesion to osteopontin versus vitronectin. Cancer Res. 62, 5336-5343 (2002).
35. Lin, Q. et al. Clinical and prognostic significance of OPN and VEGF expression in patients with non-small-cell lung cancer. Cancer Epidemiol. 39, 539-544 (2015).
36. Chakraborty, G., Jain, S. & Kundu, G. C. Osteopontin promotes vascular endothelial growth factor-dependent breast tumor growth and angiogenesis via autocrine and paracrine mechanisms. Cancer Res. 68, 152-161 (2008).
37. Shi, L. & Wang, X. Role of osteopontin in lung cancer evolution and heterogeneity. Semin. Cell. Dev. Biol. 64, 40-47 (2016).
38. Shojaei, F. et al. Osteopontin induces growth of metastatic tumors in a preclinical model of non-small lung cancer. J. Exp. Clin. Cancer Res. 31, 26 (2012).
39. Kang, C. G., Han, H. J., Lee, H. J., Kim, S. H. & Lee, E. O. Rho-associated kinase signaling is required for osteopontin-induced cell invasion through inactivating cofilin in human non-small cell lung cancer cell lines. Bioorg. Med. Chem. Lett. 25, 1956-1960 (2015).
40. Cho, W. Y. et al. Suppression of tumor growth in lung cancer xenograft model mice by poly(sorbitol-co-PEI)-mediated delivery of osteopontin siRNA. Eur. J. Pharm. Biopharm. 94, 450-462 (2015).
41. Funakoshi, T., Lee, C. H. & Hsieh, J. J. A systematic review of predictive and prognostic biomarkers for VEGF-targeted therapy in renal cell carcinoma. Cancer Treat. Rev. 40, 533-547 (2014).
42. Tran, H. T. et al. Prognostic or predictive plasma cytokines and angiogenic factors for patients treated with pazopanib for metastatic renal-cell cancer: A retrospective analysis of phase 2 and phase 3 trials. Lancet Oncol. 13, 827-837 (2012).
43. Rabjerg, M. et al. Molecular characterization of clear cell renal cell carcinoma identifies CSNK2A1, SPP1 and DEFB1 as promising novel prognostic markers. APMIS 124, 372-383 (2016).
44. Gotoh, M., Sakamoto, M., Kanetaka, K., Chuuma, M. & Hirohashi, S. Overexpression of osteopontin in hepatocellular carcinoma. Pathol. Int. 52, 19-24 (2002).
45. Pan, H. W. et al. Overexpression of osteopontin is associated with intrahepatic metastasis, early recurrence, and poorer prognosis of surgically resected hepatocellular carcinoma. Cancer 98, 119-127 (2003).
46. Ye, Q. H. et al. Predicting hepatitis B virus-positive metastatic hepatocellular carcinomas using gene expression profiling and supervised machine learning. Nat. Med. 9, 416-423 (2003).
47. Huang, J. et al. Correlation between genomic DNA copy number alterations and transcriptional expression in hepatitis B virus-associated hepatocellular carcinoma. FEBS Lett. 580, 3571-3581 (2006).
48. Kim, J. et al. Elevated plasma osteopontin levels in patients with hepatocellular carcinoma. Am. J. Gastroenterol. 101, 2051-2059 (2006).
49. Zhang, H. et al. The prognostic significance of preoperative plasma levels of osteopontin in patients with hepatocellular carcinoma. J. Cancer Res. Clin. Oncol. 132, 709-717 (2006).
50. Shang, S. et al. Identification of osteopontin as a novel marker for early hepatocellular carcinoma. Hepatology 55, 483-490 (2012).
51. Lee, Y. J. & Jang, B. K. Can combination of osteopontin and peritumorinfiltrating macrophages be a prognostic marker of early-stage hepatocellular carcinoma? Hepatobiliary Surg. Nutr. 3, 57-59 (2014).
52. Chen, R. X., Xia, Y. H., Xue, T. C., Zhang, H. & Ye, S. L. Down-regulation of osteopontin inhibits metastasis of hepatocellular carcinoma cells via a mechanism involving MMP-2 and uPA. Oncol. Rep. 25, 803-808 (2011).
53. Sun, B. S. et al. Lentiviral-mediated miRNA against osteopontin suppresses tumor growth and metastasis of human hepatocellular carcinoma. Hepatology 48, 1834-1842 (2008).
54. Bhattacharya, S. D. et al. Micro-RNA-181a regulates osteopontin-dependent metastatic function in hepatocellular cancer cell lines. Surgery 148, 291-297 (2010).
55. Jemal, A. et al. Global cancer statistics. Cancer J. Clin. 61, 69-90 (2011).
56. Coppola, D. et al. Correlation of osteopontin protein expression and pathological stage across a wide variety of tumor histologies. Clin. Cancer Res. 10, 184-190 (2004).
57. Park, M. G. et al. The value of plasma osteopontin levels as a predictive factor of disease stage and recurrence in patients with bladder urothelial carcinoma: A prospective study. Kaohsiung. J. Med. Sci. 28, 526-530 (2012).
58. Ke, H. L. et al. Osteopontin overexpression predicts poor prognosis of upper urinary tract urothelial carcinoma. Urol. Oncol. 29, 703-709 (2011).
59. Tuck, A. B. et al. Osteopontin and p53 expression are associated with tumor progression in a case of synchronous, bilateral, invasive mammary carcinomas. Arch. Pathol. Lab. Med. 121, 578-584 (1997).
60. Tuck, A. B. et al. Osteopontin expression in a group of lymph node negative breast cancer patients. Int. J. Cancer 79, 502-508 (1998).
61. Mitas, M. et al. Quantitative real-time RT-PCR detection of breast cancer micrometastasis using a multigene marker panel. Int. J. Cancer 93, 162-171 (2001).
62. Rudland, P. S. et al. Prognostic significance of the metastasis-associated protein osteopontin in human breast cancer. Cancer Res. 62, 3417-3427 (2002).
63. Brown, L. F. et al. Osteopontin expression and distribution in human carcinomas. Am. J. Pathol. 145, 610-623 (1994).
64. Tuck, A. B. & Chambers, A. F. The role of osteopontin in breast cancer: clinical and experimental studies. J. Mammary Gland. Biol. Neoplasia. 6, 419-429 (2001).
65. Tuck, A. B., Elliott, B. E., Hota, C., Tremblay, E. & Chambers, A. F. Osteopontininduced, integrin-dependent migration of human mammary epithelial cells involves activation of the hepatocyte growth factor receptor (Met). J. Cell. Biochem. 78, 465-475 (2000).
66. Noti, J. D. Adherence to osteopontin via alphavbeta3 suppresses phorbol ester-mediated apoptosis in MCF-7 breast cancer cells that overexpress protein kinase C-alpha. Int. J. Oncol. 17, 1237-1243 (2000).
67. Wu, I. C. et al. Osteopontin expression in squamous cell cancer of the esophagus. World J. Surg. 32, 1989-1995 (2008).
68. Ito, T. et al. An inducible short-hairpin RNA vector against osteopontin reduces metastatic potential of human esophageal squamous cell carcinoma in vitro and in vivo. Clin. Cancer Res. 12, 1308-1316 (2006).
69. Kolb, A. et al. Osteopontin influences the invasiveness of pancreatic cancer cells and is increased in neoplastic and inflammatory conditions. Cancer Biol. Ther. 4, 740-746 (2005).
70. Zhivkova-Galunska, M. et al. Osteopontin but not osteonectin favors the metastatic growth of pancreatic cancer cell lines. Cancer Biol. Ther. 10, 54-64 (2010).
71. Ohno, K. et al. Inhibition of osteopontin reduces liver metastasis of human pancreatic cancer xenografts injected into the spleen in a mouse model. Surg. Today 40, 347-356 (2010).
72. Lazar, M. et al. Involvement of osteopontin in the matrix-degrading and proangiogenic changes mediated by nicotine in pancreatic cancer cells. J. Gastrointest. Surg. 14, 1566-1577 (2010).
73. Koopmann, J. et al. Evaluation of osteopontin as biomarker for pancreatic adenocarcinoma. Cancer Epidemiol. Biomark. Prev. 13, 487-491 (2004).
74. Poruk, K. E. et al. Serum osteopontin and tissue inhibitor of metalloproteinase 1 as diagnostic and prognostic biomarkers for pancreatic adenocarcinoma. Pancreas 42, 193-197 (2013).
75. Parsonnet, J. et al. Helicobacter pylori infection and the risk of gastric carcinoma. N. Engl. J. Med. 325, 1127-1131 (1991).
76. Lee, S. H. et al. Ablation of osteopontin suppresses N-methyl-N-nitrosourea and Helicobacter pylori-induced gastric cancer development in mice. Carcinogenesis 36, 1550-1560 (2015).
77. Bromberg, J. & Darnell, J. E. Jr. The role of STATs in transcriptional control and their impact on cellular function. Oncogene 19, 2468-2473 (2000).
78. Xu, W., Liu, L. Z., Loizidou, M., Ahmed, M. & Charles, I. G. The role of nitric oxide in cancer. Cell. Res. 12, 311-320 (2002).
79. Vakkala, M. et al. Inducible nitric oxide synthase expression, apoptosis, and angiogenesis in in situ and invasive breast carcinomas. Clin. Cancer Res. 6, 2408-2416 (2000).
80. Tang, X. et al. Osteopontin splice variants differentially exert clinicopathological features and biological functions in gastric cancer. Int. J. Biol. Sci. 9, 55-66 (2013).
81. Liu, J. et al. Osteopontin promotes the progression of gastric cancer through the NF-kappaB pathway regulated by the MAPK and PI3K. Int. J. Oncol. 45, 282-290 (2014).
82. Wang, Z.M., Cui, Y. H., Li, W., Chen, S. Y. & Liu, T. S. Lentiviral-mediated siRNA targeted against osteopontin suppresses the growth and metastasis of gastric cancer cells. Oncol. Rep. 25, 997-1003 (2011).
83. Song, G. et al. Osteopontin promotes gastric cancer metastasis by augmenting cell survival and invasion through Akt-mediated HIF-1alpha upregulation and MMP9 activation. J. Cell. Mol. Med. 13, 1706-1718 (2009).
84. Rao, G. et al. Reciprocal interactions between tumor-associated macrophages and CD44-positive cancer cells via osteopontin/CD44 promote tumorigenicity in colorectal cancer. Clin. Cancer Res. 19, 785-797 (2013).
85. Ng, L. et al. Osteopontin overexpression induced tumor progression and chemoresistance to oxaliplatin through induction of stem-like properties in human colorectal cancer. Stem Cells Int. 2015, 247892 (2015).
86. Likui, W., Hong, W. & Shuwen, Z. Clinical significance of the upregulated osteopontin mRNA expression in human colorectal cancer. J. Gastrointest. Surg. 14, 74-81 (2010).
87. Li, J., Yang, G. Z., Zhu, Z.M., Zhou, Z. Y. & Li, L. Osteopontin is overexpressed in colorectal carcinoma and is correlated with P53 by immunohistochemistry. Exp. Ther. Med. 3, 621-624 (2012).
88. Sun, L. et al. Combination of haptoglobin and osteopontin could predict colorectal cancer hepatic metastasis. Ann. Surg. Oncol. 19, 2411-2419 (2012).
89. Zhao, M., Liang, F., Zhang, B., Yan, W. & Zhang, J. The impact of osteopontin on prognosis and clinicopathology of colorectal cancer patients: A systematic meta-analysis. Sci. Rep. 5, 12713 (2015).
90. Khodavirdi, A. C. et al. Increased expression of osteopontin contributes to the progression of prostate cancer. Cancer Res. 66, 883-888 (2006).
91. Thalmann, G. N. et al. Osteopontin: possible role in prostate cancer progression. Clin. Cancer Res. 5, 2271-2277 (1999).
92. Desai, B., Rogers, M. J. & Chellaiah, M. A. Mechanisms of osteopontin and CD44 as metastatic principles in prostate cancer cells. Mol. Cancer 6, 18 (2007).
93. Desai, B., Ma, T. & Chellaiah, M. A. Invadopodia and matrix degradation, a new property of prostate cancer cells during migration and invasion. J. Biol. Chem. 283, 13856-13866 (2008).
94. Gupta, A., Zhou, C. Q. & Chellaiah, M. A. Osteopontin and MMP9: Associations with VEGF Expression/Secretion and Angiogenesis in PC3 Prostate Cancer Cells. Cancers 5, 617-638 (2013).
95. Robertson, B. W., Bonsal, L. & Chellaiah, M. A. Regulation of Erk1/2 activation by osteopontin in PC3 human prostate cancer cells. Mol. Cancer 9, 260 (2010).
96. Jain, S., Chakraborty, G. & Kundu, G. C. The crucial role of cyclooxygenase-2 in osteopontin-induced protein kinase C alpha/c-Src/IkappaB kinase alpha/ beta-dependent prostate tumor progression and angiogenesis. Cancer Res. 66, 6638-6648 (2006).
97. Angelucci, A. et al. Osteopontin enhances the cell proliferation induced by the epidermal growth factor in human prostate cancer cells. Prostate 59, 157-166 (2004).
98. Wang, Y. D., Chen, H., Liu, H. Q. & Hao, M. Correlation between ovarian neoplasm and serum levels of osteopontin: A meta-analysis. Tumour Biol. 35, 11799-11808 (2014).
99. Tilli, T. M. et al. Osteopontin-c splicing isoform contributes to ovarian cancer progression. Mol. Cancer Res. 9, 280-293 (2011).
100. Tilli, T. M., Bellahcene, A., Castronovo, V. & Gimba, E. R. Changes in the transcriptional profile in response to overexpression of the osteopontin-c splice isoform in ovarian (OvCar-3) and prostate (PC-3) cancer cell lines. BMC Cancer 14, 433 (2014).
101. Sugiyama, T. et al. Clinical characteristics of clear cell carcinoma of the ovary: A distinct histologic type with poor prognosis and resistance to platinumbased chemotherapy. Cancer 88, 2584-2589 (2000).
102. Matsuura, M., Suzuki, T. & Saito, T. Osteopontin is a new target molecule for ovarian clear cell carcinoma therapy. Cancer Sci. 101, 1828-1833 (2010).
103. Kato, N. & Motoyama, T. Overexpression of osteopontin in clear cell carcinoma of the ovary: close association with HNF-1beta expression. Histopathology 52, 682-688 (2008).
104. Matsuura, M. et al. Statin-mediated reduction of osteopontin expression induces apoptosis and cell growth arrest in ovarian clear cell carcinoma. Oncol. Rep. 25, 41-47 (2011).
105. Johnston, N. I. et al. Osteopontin as a target for cancer therapy. Front. Biosci. 13, 4361-4372 (2008).
106. Weber, G. F. The metastasis gene osteopontin: A candidate target for cancer therapy. Biochim. Biophys. Acta 1552, 61-85 (2001).
107. Kon, S. et al. Antibodies to different peptides in osteopontin reveal complexities in the various secreted forms. J. Cell. Biochem. 77, 487-498 (2000).
108. Likui, W., Hong, W., Shuwen, Z., Yuangang, Y. & Yan, W. The potential of osteopontin as a therapeutic target for human colorectal cancer. J. Gastrointest. Surg. 15, 652-659 (2011).
109. Bandopadhyay, M. et al. Osteopontin as a therapeutic target for cancer. Expert. Opin. Ther. Targets 18, 883-895 (2014).
110. Wu, Y., Denhardt, D. T. & Rittling, S. R. Osteopontin is required for full expression of the transformed phenotype by the ras oncogene. Br. J. Cancer 83, 156-163 (2000).
111. Nemoto, H. et al. Osteopontin deficiency reduces experimental tumor cell metastasis to bone and soft tissues. J. Bone Miner. Res. 16, 652-659 (2001).
112. Wu, X. L. et al. Osteopontin knockdown suppresses the growth and angiogenesis of colon cancer cells. World J. Gastroenterol. 20, 10440-10448 (2014).
113. Yang, L. et al. Silencing of osteopontin promotes the radiosensitivity of breast cancer cells by reducing the expression of hypoxia inducible factor 1 and vascular endothelial growth factor. Chin. Med. J. 125, 293-299 (2012).
114. Mi, Z. et al. Osteopontin promotes CCL5-mesenchymal stromal cell-mediated breast cancer metastasis. Carcinogenesis 32, 477-487 (2011).
115. Kumar, S. et al. Andrographolide inhibits osteopontin expression and breast tumor growth through down regulation of PI3 kinase/Akt signaling pathway. Curr. Mol. Med. 12, 952-966 (2012).
116. Mi, Z. et al. RNA aptamer blockade of osteopontin inhibits growth and metastasis of MDA-MB231 breast cancer cells. Mol. Ther. 17, 153-161 (2009).
117. Kumar, V., Behera, R., Lohite, K., Karnik, S. & Kundu, G. C. p38 Kinase is crucial for osteopontin-induced furin expression that supports cervical cancer progression. Cancer Res. 70, 10381-10391 (2010).
118. Saleh, S., Thompson, D. E., McConkey, J., Murray, P. & Moorehead, R. A. Osteopontin regulates proliferation, apoptosis, and migration of murine claudin-low mammary tumor cells. BMC Cancer 16, 359 (2016).
119. Zhang, H. et al. Osteopontin knockdown inhibits aαv, β3 integrin-induced cell migration and invasion and promotes apoptosis of breast cancer cells by inducing autophagy and inactivating the PI3K/Akt/mTOR pathway. Cell. Physiol. Biochem. 33, 991-1002 (2014).
120. Zagani, R. et al. Cyclooxygenase-2 inhibitors down-regulate osteopontin and Nr4A2-new therapeutic targets for colorectal cancers. Gastroenterology 137, 1358-1366 (2009). e1351-1353.
121. Sharma, P., Kumar, S. & Kundu, G. C. Transcriptional regulation of human osteopontin promoter by histone deacetylase inhibitor, trichostatin A in cervical cancer cells. Mol. Cancer 9, 178 (2010).
122. Lv, J. et al. Effects and mechanisms of curcumin and basil polysaccharide on the invasion of SKOV3 cells and dendritic cells. Mol. Med. Rep. 8, 1580-1586 (2013).
123. Mason, C. K. et al. Agelastatin A: A novel inhibitor of osteopontin-mediated adhesion, invasion, and colony formation. Mol. Cancer Ther. 7, 548-558 (2008).
124. Dai, J. et al. A humanized anti-osteopontin antibody inhibits breast cancer growth and metastasis in vivo. Cancer Immunol. Immunother. 59, 355-366 (2010).
125. Ahmed, M. & Kundu, G. C. Osteopontin selectively regulates p70S6K/mTOR phosphorylation leading to NF-kappaB dependent AP-1-mediated ICAM-1 expression in breast cancer cells. Mol. Cancer 9, 101 (2010).
126. Teramoto, H. et al. Autocrine activation of an osteopontin-CD44-Rac pathway enhances invasion and transformation by H-RasV12. Oncogene 24, 489-501 (2005).