Research progress on signaling pathways related to pulmonary metastasis of osteosarcoma_West China Medical Journal

Authors：

CHEN Jian ¹ , LI Ye ¹ ,  XIE Kegong ²

1. Graduate School, Youjiang Medical University for Nationalities, Baise, Guangxi 533000, P. R. China;
2. Department of Osteological Surgery, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi 533000, P. R. China;

Corresponding?author：

XIE Kegong, Email: 821745104@qq.com

Keywords：

Osteosarcoma; pulmonary metastasis; signaling pathway; research progress

DOI：

10.7507/1002-0179.202010134

Video：

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Abstract Full text Figures/Tables Video References Cited by

As the most common primary malignant bone tumor in children and adolescents, osteosarcoma has the characteristics of high malignancy, easy metastasis and poor prognosis. The recurrence, metastasis and multi-drug resistance of osteosarcoma are the main problems that limit the therapeutic effect and survival rate of osteosarcoma. Among them, lung metastasis is often the main target organ for distant metastasis of osteosarcoma. In recent years, people have paid attention to the signaling pathway of the occurrence and development of osteosarcoma and made in-depth studies on its mechanism. A variety of relevant signaling pathways have been constantly clarified. At present, there is still a lack of systematic and multi-directional exploration and summary on the signaling pathway related to the pulmonary metastasis of osteosarcoma. This paper explores the new direction of targeted therapy for osteosarcoma by elucidating the relationship between the signaling pathway associated with osteosarcoma and the pulmonary metastasis of osteosarcoma.

Citation： CHEN Jian, LI Ye, XIE Kegong. Research progress on signaling pathways related to pulmonary metastasis of osteosarcoma. West China Medical Journal, 2022, 37(2): 306-312. doi: 10.7507/1002-0179.202010134 Copy

1.	Rickel K, Fang F, Tao J. Molecular genetics of osteosarcoma. Bone, 2017, 102: 69-79.
2.	Isakoff MS, Bielack SS, Meltzer P, et al. Osteosarcoma: current treatment and a collaborative pathway to success. J Clin Oncol, 2015, 33(27): 3029-3035.
3.	王顯陽, 常君麗, 施杞, 等. 骨肉瘤相關信號通路的研究進展. 中國癌癥防治雜志, 2015, 7(1): 52-55.
4.	卓航宇, 唐毓金. 骨肉瘤發生發展相關信號通路研究進展. 右江醫學, 2019, 47(6): 406-410.
5.	Wu PK, Chen WM, Chen CF, et al. Primary osteogenic sarcoma with pulmonary metastasis: clinical results and prognostic factors in 91 patients. Jpn J Clin Oncol, 2009, 39(8): 514-522.
6.	Shaikh AB, Li F, Li M, et al. Present advances and future perspectives of molecular targeted therapy for osteosarcoma. Int J Mol Sci, 2016, 17(4): 506.
7.	史夢婕, 邵松軍, 李潔媚, 等. Hippo 通路與腫瘤相關性研究進展. 中國細胞生物學學報, 2014, 36(3): 361-365.
8.	Taha Z, Janse van Rensburg HJ, Yang X. The hippo pathway: immunity and cancer. Cancers (Basel), 2018, 10(4): 94.
9.	Hong AW, Meng Z, Guan KL. The hippo pathway in intestinal regeneration and disease. Nat Rev Gastroenterol Hepatol, 2016, 13(6): 324-337.
10.	Kim MH, Kim J. Role of YAP/TAZ transcriptional regulators in resistance to anti-cancer therapies. Cell Mol Life Sci, 2017, 74(8): 1457-1474.
11.	Ahmed AA, Mohamed AD, Gener M, et al. YAP and the hippo pathway in pediatric cancer. Mol Cell Oncol, 2017, 4(3): e1295127.
12.	Deel MD, Li JJ, Crose LE, et al. A review: molecular aberrations within hippo signaling in bone and soft-tissue sarcomas. Front Oncol, 2015, 5: 190.
13.	Luu AK, Schott CR, Jones R, et al. An evaluation of TAZ and YAP crosstalk with TGFβ signalling in canine osteosarcoma suggests involvement of hippo signalling in disease progression. BMC Vet Res, 2018, 14(1): 365.
14.	Fullenkamp CA, Hall SL, Jaber OI, et al. TAZ and YAP are frequently activated oncoproteins in sarcomas. Oncotarget, 2016, 7(21): 30094-30108.
15.	Bouvier C, Macagno N, Nguyen Q, et al. Prognostic value of the hippo pathway transcriptional coactivators YAP/TAZ and β1-integrin in conventional osteosarcoma. Oncotarget, 2016, 7(40): 64702-64710.
16.	Maurizi G, Verma N, Gadi A, et al. Sox2 is required for tumor development and cancer cell proliferation in osteosarcoma. Oncogene, 2018, 37(33): 4626-4632.
17.	Zhou Y, Jin Q, Xiao W, et al. Tankyrase1 antisense oligodeoxynucleotides suppress the proliferation, migration and invasion through hippo/YAP pathway in human osteosarcoma cells. Pathol Res Pract, 2019, 215(6): 152381.
18.	Fruman DA, Chiu H, Hopkins BD, et al. The PI3K pathway in human disease. Cell, 2017, 170(4): 605-635.
19.	Keppler-Noreuil KM, Parker VE, Darling TN, et al. Somatic overgrowth disorders of the PI3K/AKT/mTOR pathway & therapeutic strategies. Am J Med Genet C Semin Med Genet, 2016, 172(4): 402-421.
20.	Tan AC. Targeting the PI3K/Akt/mTOR pathway in non‐small cell lung cancer (NSCLC). Thoracic Cancer, 2020, 11(3): 511-518.
21.	Papa A, Wan L, Bonora M, et al. Cancer-Associated PTEN mutants act in a dominant-negative manner to suppress PTEN protein function. Cell, 2014, 157(3): 595-610.
22.	Chalhoub N, Baker SJ. PTEN and the PI3-kinase pathway in cancer. Annu Rev Pathol, 2009, 4: 127-150.
23.	Saxton RA, Sabatini DM. mTOR signaling in growth, metabolism, and disease. Cell, 2017, 169(2): 361-371.
24.	Perry JA, Kiezun A, Tonzi P, et al. Complementary genomic approaches highlight the PI3K/mTOR pathway as a common vulnerability in osteosarcoma. Proc Natl Acad Sci USA, 2014, 111(51): E5564-E5573.
25.	Keremu A, Maimaiti X, Aimaiti A, et al. NRSN2 promotes osteosarcoma cell proliferation and growth through PI3K/AKT/MTOR and Wnt/β-catenin signaling. Am J Cancer Res, 2017, 7(3): 565-573.
26.	趙郭盛. 印跡基因 TSSC3 調控自噬抑制骨肉瘤成瘤和轉移的作用及分子機制研究. 重慶: 重慶醫科大學, 2019.
27.	Zhao GS, Gao ZR, Zhang Q, et al. TSSC3 promotes autophagy via inactivating the src-mediated PI3K/AKT/mTOR pathway to suppress tumorigenesis and metastasis in osteosarcoma, and predicts a favorable prognosis. J Exp Clin Cancer Res, 2018, 37(1): 188.
28.	Li ZZ, Wang YL, Yu YH, et al. Aclidinium bromide inhibits proliferation of osteosarcoma cells through regulation of PI3K/AKT pathway. Eur Rev Med Pharmacol Sci, 2019, 23(1): 105-112.
29.	張一奇, 劉子云, 付勤. Notch 通路在骨疾病領域的研究進展. 解剖科學進展, 2018, 24(4): 411-414.
30.	Aster JC, Pear WS, Blacklow SC. The varied roles of Notch in cancer. Annu Rev Pathol, 2017, 12: 245-275.
31.	Fukusumi T, Califano JA. The Notch pathway in head and neck squamous cell carcinoma. J Dent Res, 2018, 97(6): 645-653.
32.	Vieceli Dalla Sega F, Fortini F, Aquila G, et al. Notch signaling regulates immune responses in atherosclerosis. Front Immunol, 2019, 10: 1130.
33.	Vinson KE, George DC, Fender AW, et al. The Notch pathway in colorectal cancer. Int J Cancer, 2016, 138(8): 1835-1842.
34.	Arruga F, Vaisitti T, Deaglio S. The Notch pathway and its mutations in mature b cell malignancies. Front Oncol, 2018, 8: 550.
35.	Rodrigues C, Joy LR, Sachithanandan SP, et al. Notch signalling in cervical cancer. Exp Cell Res, 2019, 385(2): 111682.
36.	Hu Y, Su H, Li X, et al. The Notch ligand JAGGED2 promotes pancreatic cancer metastasis independent of Notch signaling activation. Mol Cancer Ther, 2015, 14(1): 289-297.
37.	Kranenburg O. Prometastatic Notch signaling in colon cancer. Cancer Discov, 2015, 5(2): 115-117.
38.	Adamopoulos C, Gargalionis AN, Basdra EK, et al. Deciphering signaling networks in osteosarcoma pathobiology. Exp Biol Med (Maywood), 2016, 241(12): 1296-1305.
39.	Liu P, Man Y, Wang Y, et al. Mechanism of BMP9 promotes growth of osteosarcoma mediated by the Notch signaling pathway. Oncol Lett, 2016, 11(2): 1367-1370.
40.	Engin F, Bertin T, Ma O, et al. Notch signaling contributes to the pathogenesis of human osteosarcomas. Hum Mol Genet, 2009, 18(8): 1464-1470.
41.	Tao J, Jiang MM, Jiang L, et al. Notch activation as a driver of osteogenic sarcoma. Cancer Cell, 2014, 26(3): 390-401.
42.	Mu X, Agarwal R, March D, et al. Notch signaling mediates skeletal muscle atrophy in cancer cachexia caused by osteosarcoma. Sarcoma, 2016: 3758162.
43.	Nusse R, Clevers H. Wnt/β-catenin signaling, disease, and emerging therapeutic modalities. Cell, 2017, 169(6): 985-999.
44.	Taciak B, Pruszynska I, Kiraga L, et al. Wnt signaling pathway in development and cancer. J Physiol Pharmacol, 2018, 69(2): 185-196.
45.	Nusse R, Varmus HE. Many tumors induced by the mouse mammary tumor virus contain a provirus integrated in the same region of the host genome. Cell, 1982, 31(1): 99-109.
46.	Zhan T, Rindtorff N, Boutros M. Wnt signaling in cancer. Oncogene, 2017, 36(11): 1461-1473.
47.	Fang F, VanCleave A, Helmuth R, et al. Targeting the Wnt/β-catenin pathway in human osteosarcoma cells. Oncotarget, 2018, 9(95): 36780-36792.
48.	Chang J, Li Y, Wang X, et al. Polyphyllin I suppresses human osteosarcoma growth by inactivation of Wnt/β-catenin pathway in vitro and in vivo. Sci Rep, 2017, 7(1): 7605.
49.	Jiang K, Li S, Li L, et al. Wnt6 is an effective marker for osteosarcoma diagnosis and prognosis. Medicine (Baltimore), 2018, 97(46): e13011.
50.	Chen C, Zhao M , Tian A, et al. Aberrant activation of Wnt/β-catenin signaling drives proliferation of bone sarcoma cells. Oncotarget, 2015, 6(19): 17570-17583.
51.	Lambert AW, Pattabiraman DR, Weinberg RA. Emerging biological principles of metastasis. Cell, 2017, 168(4): 670-691.
52.	Stella GM, Kolling S, Benvenuti S, et al. Lung-seeking metastases. Cancers (Basel), 2019, 11(7): 1010.
53.	Zhao X, Wen X, Wei W, et al. Clinical characteristics and prognoses of patients treated surgically for metastatic lung tumors. Oncotarget, 2017, 8(28): 46491-46497.
54.	Fan TM, Roberts RD, Lizardo MM. Understanding and modeling metastasis biology to improve therapeutic strategies for combating osteosarcoma progression. Front Oncol, 2020, 10: 13.
55.	Liu K, Ni JD, Li WZ, et al. The Sp1/FOXC1/HOTTIP/LATS2/YAP/β-catenin cascade promotes malignant and metastatic progression of osteosarcoma. Mol Oncol, 2020, 14(10): 2678-2695.
56.	Gvozdenovic A, Boro A, Meier D, et al. Targeting αvβ3 and αvβ5 integrins inhibits pulmonary metastasis in an intratibial xenograft osteosarcoma mouse model. Oncotarget, 2016, 7(34): 55141-55154.
57.	陳善明, 平安松, 劉鴻, 等. 整合素αvβ3 和αvβ5 在發生肺轉移的骨肉瘤組織的表達及其臨床意義. 中華實驗外科雜志, 2018, 35(2): 350-352.
58.	隋吉生, 邵國強, 張露露, 等. 整合素αvβ3 受體靶向顯像骨肉瘤和診治肺轉移的初步研究. 中國修復重建外科雜志, 2019, 33(2): 170-176.
59.	Song R, Tian K, Wang W, et al. P53 suppresses cell proliferation, metastasis, and angiogenesis of osteosarcoma through inhibition of the PI3K/AKT/mTOR pathway. Int J Surg, 2015, 20: 80-87.
60.	Sabile AA, Arlt MJ, Muff R, et al. Caprin-1, a novel cyr61-interacting protein, promotes osteosarcoma tumor growth and lung metastasis in mice. Biochim Biophys Acta, 2013, 1832(8): 1173-1182.
61.	Ma H, Su R, Feng H, et al. Long noncoding RNA UCA1 promotes osteosarcoma metastasis through CREB1-mediated epithelial-mesenchymal transition and activating PI3K/AKT/mTOR pathway. J Bone Oncol, 2019, 16: e100228.
62.	Hughes DP. How the Notch pathway contributes to the ability of osteosarcoma cells to metastasize. Cancer Treat Res, 2009, 152: 479-496.
63.	Tang XF, Cao Y, Peng DB, et al. Overexpression of Notch3 is associated with metastasis and poor prognosis in osteosarcoma patients. Cancer Manag Res, 2019, 11: 547-559.
64.	Jin H, Luo S, Wang Y, et al. miR-135b stimulates osteosarcoma recurrence and lung metastasis via Notch and Wnt/β-catenin signaling. Mol Ther Nucleic Acids, 2017, 8(1): 111-122.
65.	Liu J, Zhang Y, Xu R, et al. PI3K/AKT-dependent phosphorylation of GSK3β and activation of RhoA regulate Wnt5a-induced gastric cancer cell migration. Cell Signal, 2013, 25(2): 447-456.
66.	劉廣臣. 趨化因子 CXCL6 與其受體 CXCR2 調控β-catenin 促進骨肉瘤轉移機制的研究. 長春: 吉林大學, 2018.
67.	梁爽. RIPK4、β-catenin 和 P-gp 在骨肉瘤中的表達及臨床意義. 中國療養醫學, 2019, 28(8): 795-797.
68.	Nomura M, Rainusso N, Lee YC, et al. Tegavivint and the β-catenin/ALDH axis in chemotherapy-resistant and metastatic osteosarcoma. J Natl Cancer Inst, 2019, 111(11): 1216-1227.
69.	Rubin EM, Guo Y, Tu K, et al. Wnt inhibitory factor 1 decreases tumorigenesis and metastasis in osteosarcoma. Mol Cancer Ther, 2010, 9(3): 731-741.
70.	Lin CH, Guo Y, Ghaffa S, et al. Dkk-3, a secreted Wnt antagonist, suppresses tumorigenic potential and pulmonary metastasis in osteosarcoma. Sarcoma, 2013: e147541.

1. Rickel K, Fang F, Tao J. Molecular genetics of osteosarcoma. Bone, 2017, 102: 69-79.
2. Isakoff MS, Bielack SS, Meltzer P, et al. Osteosarcoma: current treatment and a collaborative pathway to success. J Clin Oncol, 2015, 33(27): 3029-3035.
3. 王顯陽, 常君麗, 施杞, 等. 骨肉瘤相關信號通路的研究進展. 中國癌癥防治雜志, 2015, 7(1): 52-55.
4. 卓航宇, 唐毓金. 骨肉瘤發生發展相關信號通路研究進展. 右江醫學, 2019, 47(6): 406-410.
5. Wu PK, Chen WM, Chen CF, et al. Primary osteogenic sarcoma with pulmonary metastasis: clinical results and prognostic factors in 91 patients. Jpn J Clin Oncol, 2009, 39(8): 514-522.
6. Shaikh AB, Li F, Li M, et al. Present advances and future perspectives of molecular targeted therapy for osteosarcoma. Int J Mol Sci, 2016, 17(4): 506.
7. 史夢婕, 邵松軍, 李潔媚, 等. Hippo 通路與腫瘤相關性研究進展. 中國細胞生物學學報, 2014, 36(3): 361-365.
8. Taha Z, Janse van Rensburg HJ, Yang X. The hippo pathway: immunity and cancer. Cancers (Basel), 2018, 10(4): 94.
9. Hong AW, Meng Z, Guan KL. The hippo pathway in intestinal regeneration and disease. Nat Rev Gastroenterol Hepatol, 2016, 13(6): 324-337.
10. Kim MH, Kim J. Role of YAP/TAZ transcriptional regulators in resistance to anti-cancer therapies. Cell Mol Life Sci, 2017, 74(8): 1457-1474.
11. Ahmed AA, Mohamed AD, Gener M, et al. YAP and the hippo pathway in pediatric cancer. Mol Cell Oncol, 2017, 4(3): e1295127.
12. Deel MD, Li JJ, Crose LE, et al. A review: molecular aberrations within hippo signaling in bone and soft-tissue sarcomas. Front Oncol, 2015, 5: 190.
13. Luu AK, Schott CR, Jones R, et al. An evaluation of TAZ and YAP crosstalk with TGFβ signalling in canine osteosarcoma suggests involvement of hippo signalling in disease progression. BMC Vet Res, 2018, 14(1): 365.
14. Fullenkamp CA, Hall SL, Jaber OI, et al. TAZ and YAP are frequently activated oncoproteins in sarcomas. Oncotarget, 2016, 7(21): 30094-30108.
15. Bouvier C, Macagno N, Nguyen Q, et al. Prognostic value of the hippo pathway transcriptional coactivators YAP/TAZ and β1-integrin in conventional osteosarcoma. Oncotarget, 2016, 7(40): 64702-64710.
16. Maurizi G, Verma N, Gadi A, et al. Sox2 is required for tumor development and cancer cell proliferation in osteosarcoma. Oncogene, 2018, 37(33): 4626-4632.
17. Zhou Y, Jin Q, Xiao W, et al. Tankyrase1 antisense oligodeoxynucleotides suppress the proliferation, migration and invasion through hippo/YAP pathway in human osteosarcoma cells. Pathol Res Pract, 2019, 215(6): 152381.
18. Fruman DA, Chiu H, Hopkins BD, et al. The PI3K pathway in human disease. Cell, 2017, 170(4): 605-635.
19. Keppler-Noreuil KM, Parker VE, Darling TN, et al. Somatic overgrowth disorders of the PI3K/AKT/mTOR pathway & therapeutic strategies. Am J Med Genet C Semin Med Genet, 2016, 172(4): 402-421.
20. Tan AC. Targeting the PI3K/Akt/mTOR pathway in non‐small cell lung cancer (NSCLC). Thoracic Cancer, 2020, 11(3): 511-518.
21. Papa A, Wan L, Bonora M, et al. Cancer-Associated PTEN mutants act in a dominant-negative manner to suppress PTEN protein function. Cell, 2014, 157(3): 595-610.
22. Chalhoub N, Baker SJ. PTEN and the PI3-kinase pathway in cancer. Annu Rev Pathol, 2009, 4: 127-150.
23. Saxton RA, Sabatini DM. mTOR signaling in growth, metabolism, and disease. Cell, 2017, 169(2): 361-371.
24. Perry JA, Kiezun A, Tonzi P, et al. Complementary genomic approaches highlight the PI3K/mTOR pathway as a common vulnerability in osteosarcoma. Proc Natl Acad Sci USA, 2014, 111(51): E5564-E5573.
25. Keremu A, Maimaiti X, Aimaiti A, et al. NRSN2 promotes osteosarcoma cell proliferation and growth through PI3K/AKT/MTOR and Wnt/β-catenin signaling. Am J Cancer Res, 2017, 7(3): 565-573.
26. 趙郭盛. 印跡基因 TSSC3 調控自噬抑制骨肉瘤成瘤和轉移的作用及分子機制研究. 重慶: 重慶醫科大學, 2019.
27. Zhao GS, Gao ZR, Zhang Q, et al. TSSC3 promotes autophagy via inactivating the src-mediated PI3K/AKT/mTOR pathway to suppress tumorigenesis and metastasis in osteosarcoma, and predicts a favorable prognosis. J Exp Clin Cancer Res, 2018, 37(1): 188.
28. Li ZZ, Wang YL, Yu YH, et al. Aclidinium bromide inhibits proliferation of osteosarcoma cells through regulation of PI3K/AKT pathway. Eur Rev Med Pharmacol Sci, 2019, 23(1): 105-112.
29. 張一奇, 劉子云, 付勤. Notch 通路在骨疾病領域的研究進展. 解剖科學進展, 2018, 24(4): 411-414.
30. Aster JC, Pear WS, Blacklow SC. The varied roles of Notch in cancer. Annu Rev Pathol, 2017, 12: 245-275.
31. Fukusumi T, Califano JA. The Notch pathway in head and neck squamous cell carcinoma. J Dent Res, 2018, 97(6): 645-653.
32. Vieceli Dalla Sega F, Fortini F, Aquila G, et al. Notch signaling regulates immune responses in atherosclerosis. Front Immunol, 2019, 10: 1130.
33. Vinson KE, George DC, Fender AW, et al. The Notch pathway in colorectal cancer. Int J Cancer, 2016, 138(8): 1835-1842.
34. Arruga F, Vaisitti T, Deaglio S. The Notch pathway and its mutations in mature b cell malignancies. Front Oncol, 2018, 8: 550.
35. Rodrigues C, Joy LR, Sachithanandan SP, et al. Notch signalling in cervical cancer. Exp Cell Res, 2019, 385(2): 111682.
36. Hu Y, Su H, Li X, et al. The Notch ligand JAGGED2 promotes pancreatic cancer metastasis independent of Notch signaling activation. Mol Cancer Ther, 2015, 14(1): 289-297.
37. Kranenburg O. Prometastatic Notch signaling in colon cancer. Cancer Discov, 2015, 5(2): 115-117.
38. Adamopoulos C, Gargalionis AN, Basdra EK, et al. Deciphering signaling networks in osteosarcoma pathobiology. Exp Biol Med (Maywood), 2016, 241(12): 1296-1305.
39. Liu P, Man Y, Wang Y, et al. Mechanism of BMP9 promotes growth of osteosarcoma mediated by the Notch signaling pathway. Oncol Lett, 2016, 11(2): 1367-1370.
40. Engin F, Bertin T, Ma O, et al. Notch signaling contributes to the pathogenesis of human osteosarcomas. Hum Mol Genet, 2009, 18(8): 1464-1470.
41. Tao J, Jiang MM, Jiang L, et al. Notch activation as a driver of osteogenic sarcoma. Cancer Cell, 2014, 26(3): 390-401.
42. Mu X, Agarwal R, March D, et al. Notch signaling mediates skeletal muscle atrophy in cancer cachexia caused by osteosarcoma. Sarcoma, 2016: 3758162.
43. Nusse R, Clevers H. Wnt/β-catenin signaling, disease, and emerging therapeutic modalities. Cell, 2017, 169(6): 985-999.
44. Taciak B, Pruszynska I, Kiraga L, et al. Wnt signaling pathway in development and cancer. J Physiol Pharmacol, 2018, 69(2): 185-196.
45. Nusse R, Varmus HE. Many tumors induced by the mouse mammary tumor virus contain a provirus integrated in the same region of the host genome. Cell, 1982, 31(1): 99-109.
46. Zhan T, Rindtorff N, Boutros M. Wnt signaling in cancer. Oncogene, 2017, 36(11): 1461-1473.
47. Fang F, VanCleave A, Helmuth R, et al. Targeting the Wnt/β-catenin pathway in human osteosarcoma cells. Oncotarget, 2018, 9(95): 36780-36792.
48. Chang J, Li Y, Wang X, et al. Polyphyllin I suppresses human osteosarcoma growth by inactivation of Wnt/β-catenin pathway in vitro and in vivo. Sci Rep, 2017, 7(1): 7605.
49. Jiang K, Li S, Li L, et al. Wnt6 is an effective marker for osteosarcoma diagnosis and prognosis. Medicine (Baltimore), 2018, 97(46): e13011.
50. Chen C, Zhao M , Tian A, et al. Aberrant activation of Wnt/β-catenin signaling drives proliferation of bone sarcoma cells. Oncotarget, 2015, 6(19): 17570-17583.
51. Lambert AW, Pattabiraman DR, Weinberg RA. Emerging biological principles of metastasis. Cell, 2017, 168(4): 670-691.
52. Stella GM, Kolling S, Benvenuti S, et al. Lung-seeking metastases. Cancers (Basel), 2019, 11(7): 1010.
53. Zhao X, Wen X, Wei W, et al. Clinical characteristics and prognoses of patients treated surgically for metastatic lung tumors. Oncotarget, 2017, 8(28): 46491-46497.
54. Fan TM, Roberts RD, Lizardo MM. Understanding and modeling metastasis biology to improve therapeutic strategies for combating osteosarcoma progression. Front Oncol, 2020, 10: 13.
55. Liu K, Ni JD, Li WZ, et al. The Sp1/FOXC1/HOTTIP/LATS2/YAP/β-catenin cascade promotes malignant and metastatic progression of osteosarcoma. Mol Oncol, 2020, 14(10): 2678-2695.
56. Gvozdenovic A, Boro A, Meier D, et al. Targeting αvβ3 and αvβ5 integrins inhibits pulmonary metastasis in an intratibial xenograft osteosarcoma mouse model. Oncotarget, 2016, 7(34): 55141-55154.
57. 陳善明, 平安松, 劉鴻, 等. 整合素αvβ3 和αvβ5 在發生肺轉移的骨肉瘤組織的表達及其臨床意義. 中華實驗外科雜志, 2018, 35(2): 350-352.
58. 隋吉生, 邵國強, 張露露, 等. 整合素αvβ3 受體靶向顯像骨肉瘤和診治肺轉移的初步研究. 中國修復重建外科雜志, 2019, 33(2): 170-176.
59. Song R, Tian K, Wang W, et al. P53 suppresses cell proliferation, metastasis, and angiogenesis of osteosarcoma through inhibition of the PI3K/AKT/mTOR pathway. Int J Surg, 2015, 20: 80-87.
60. Sabile AA, Arlt MJ, Muff R, et al. Caprin-1, a novel cyr61-interacting protein, promotes osteosarcoma tumor growth and lung metastasis in mice. Biochim Biophys Acta, 2013, 1832(8): 1173-1182.
61. Ma H, Su R, Feng H, et al. Long noncoding RNA UCA1 promotes osteosarcoma metastasis through CREB1-mediated epithelial-mesenchymal transition and activating PI3K/AKT/mTOR pathway. J Bone Oncol, 2019, 16: e100228.
62. Hughes DP. How the Notch pathway contributes to the ability of osteosarcoma cells to metastasize. Cancer Treat Res, 2009, 152: 479-496.
63. Tang XF, Cao Y, Peng DB, et al. Overexpression of Notch3 is associated with metastasis and poor prognosis in osteosarcoma patients. Cancer Manag Res, 2019, 11: 547-559.
64. Jin H, Luo S, Wang Y, et al. miR-135b stimulates osteosarcoma recurrence and lung metastasis via Notch and Wnt/β-catenin signaling. Mol Ther Nucleic Acids, 2017, 8(1): 111-122.
65. Liu J, Zhang Y, Xu R, et al. PI3K/AKT-dependent phosphorylation of GSK3β and activation of RhoA regulate Wnt5a-induced gastric cancer cell migration. Cell Signal, 2013, 25(2): 447-456.
66. 劉廣臣. 趨化因子 CXCL6 與其受體 CXCR2 調控β-catenin 促進骨肉瘤轉移機制的研究. 長春: 吉林大學, 2018.
67. 梁爽. RIPK4、β-catenin 和 P-gp 在骨肉瘤中的表達及臨床意義. 中國療養醫學, 2019, 28(8): 795-797.
68. Nomura M, Rainusso N, Lee YC, et al. Tegavivint and the β-catenin/ALDH axis in chemotherapy-resistant and metastatic osteosarcoma. J Natl Cancer Inst, 2019, 111(11): 1216-1227.
69. Rubin EM, Guo Y, Tu K, et al. Wnt inhibitory factor 1 decreases tumorigenesis and metastasis in osteosarcoma. Mol Cancer Ther, 2010, 9(3): 731-741.
70. Lin CH, Guo Y, Ghaffa S, et al. Dkk-3, a secreted Wnt antagonist, suppresses tumorigenic potential and pulmonary metastasis in osteosarcoma. Sarcoma, 2013: e147541.

West China Medical Journal

Research progress on signaling pathways related to pulmonary metastasis of osteosarcoma

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