脊索瘤分子信号通路的进展研究

力 陈(桂林医学院附属医院神经外科，中国)
震 叶(桂林医学院附属医院神经外科，中国)
少怀 夏(桂林医学院附属医院神经外科，中国)
文才 李(桂林医学院附属医院神经外科，中国)
凯伦 韦(桂林医学院附属医院神经外科，中国)
学巍 夏(桂林医学院附属医院神经外科，中国)

摘要

脊索瘤是一种胚胎脊索残余演化而来的罕见恶性骨肿瘤，其具有高度侵袭和局部浸润性，且生长的方式及位置的特殊性使完全切除肿瘤比较困难，由于脊索瘤具有化学抗性，临床上的放化疗效果不佳，且具有高复发率的存在，尚不存在有效的药物治疗方法。脊索瘤的治疗对于临床医师而言仍然是一大挑战。近年来肿瘤分子信号通路和表观遗传的研究已经在脊索瘤治疗方面已经有了一些突破性进展，其中Brachyury、SOX9、survivin、MicroRNA和表观遗传学改变等分子信号通路通过调节脊索瘤细胞增殖、迁移、侵袭等生物学活性对脊索瘤的发展产生影响。充分了解脊索瘤中分子信号通路的机制有助于临床改善预后和早期对其进行有效的分子靶向干预。积极找寻脊索瘤进展的分子信号通路对于当前脊索瘤治疗和管理至关重要，论文结合当前脊索瘤分子信号通路的研究热点进行系统的综述。

关键词

脊索瘤；信号通路；迁移；侵袭；靶向干预

参考

Walcott, B.P., et al., Chordoma: current concepts, management, and future directions[J]. Lancet Oncol, 2012(02)69-76.

Stacchiotti, S., et al., Chordoma of the mobile spine and sacrum: a retrospective analysis of a series of patients surgically treated at two referral centers[J]. Ann Surg Oncol, 2010(01):211-219.

Chambers, K.J., et al., Incidence and survival patterns of cranial chordoma in the United States. Laryngoscope, 2014(05):1097-1102.

Hao, S., et al., Protein phosphatase 2A inhibition enhances radiation sensitivity and reduces tumor growth in chordoma[J]. Neuro Oncol, 2018(06):799-809.

McMaster, M.L., et al., Chordoma: incidence and survival patterns in the United States, 1973-1995[J]. Cancer Causes Control, 2001(01):1-11.

Hu, W., et al., Lymphocyte-Related Inflammation and Immune-Based Scores Predict Prognosis of Chordoma Patients After Radical Resection[J]. Transl Oncol, 2018(02):444-449.

Barresi, V., et al., Brachyury: a diagnostic marker for the differential diagnosis of chordoma and hemangioblastoma versus neoplastic histological mimickers[J]. Dis Markers, 2014(13):514753.

Kispert, A. and B.G. Herrmann, Immunohistochemical analysis of the Brachyury protein in wild-type and mutant mouse embryos[J]. Dev Biol, 1994(01):179-193.

Otani, R., et al., Brachyury gene copy number gain and activation of the PI3K/Akt pathway: association with upregulation of oncogenic Brachyury expression in skull base chordoma[J]. J Neurosurg, 2018(05):1428-1437.

Yan, X., et al., Inhibition Of Glycogen Synthase Kinase 3 Beta Suppresses The Growth And Survival Of Skull Base Chordoma Cells By Downregulating Brachyury Expression[J]. Onco Targets Ther, 2019(12):9783-9791.

Vujovic, S., et al., Brachyury, a crucial regulator of notochordal development, is a novel biomarker for chordomas[J]. J Pathol, 2006(02):157-165.

Hu, Y., et al., Liposome-Protamine-DNA Nanoparticle-Mediated Delivery of Short Hairpin RNA Targeting Brachyury Inhibits Chordoma Cell Growth[J]. J Biomed Nanotechnol, 2016(10):1952-1961.

Gill, C.M., M. Fowkes, and R.K. Shrivastava, Emerging Therapeutic Targets in Chordomas: A Review of the Literature in the Genomic Era[J]. Neurosurgery, 2020(02):118-123.

Bowles, J., G. Schepers, and P. Koopman, Phylogeny of the SOX family of developmental transcription factors based on sequence and structural indicators[J]. Dev Biol, 2000(02):239-255.

Castillo, S.D. and M. Sanchez-Cespedes, The SOX family of genes in cancer development: biological relevance and opportunities for therapy[J]. Expert Opin Ther Targets, 2012(09):903-919.

Akiyama, H., et al., The transcription factor Sox9 has essential roles in successive steps of the chondrocyte differentiation pathway and is required for expression of Sox5 and Sox6[J]. Genes Dev, 2002(21):2813-2828.

Guo, W., et al., Slug and Sox9 cooperatively determine the mammary stem cell state[J]. Cell, 2012()5):1015-1028.

Blache, P., et al., SOX9 is an intestine crypt transcription factor, is regulated by the Wnt pathway, and represses the CDX2 and MUC2 genes[J]. J Cell Biol, 2004(01):37-47.

Vidal, V.P., et al., Sox9 is essential for outer root sheath differentiation and the formation of the hair stem cell compartment[J]. Curr Biol, 2005(15):1340-1351.

Song, S., et al., Loss of TGF-beta adaptor beta2SP activates notchsignaling and SOX9 expression in esophageal adenocarcinoma[J]. Cancer Res, 2013(07):2159-2169.

Ling, S., et al., An EGFR-ERK-SOX9 signaling cascade links urothelial development and regeneration to cancer[J]. Cancer Res, 2011(11):3812-3821.

Sun, L., et al., Epigenetic regulation of SOX9 by the NF-kappaB signaling pathway in pancreatic cancer stem cells[J]. Stem Cells, 2013(08):1454-1466.

Chen, H., et al., Expression and Therapeutic Potential of SOX9 in Chordoma[J]. Clin Cancer Res, 2017(17):5176-5186.

Jaiswal, P.K., A. Goel, and R.D. Mittal, Survivin: A molecular biomarker in cancer[J]. Indian J Med Res, 2015(04):389-397.

Ambrosini, G., C. Adida, and D.C. Altieri, A novel anti-apoptosis gene, survivin, expressed in cancer and lymphoma[J]. Nat Med, 1997(08):917-921.

Chen, C., et al., High expression of survivin in sacral chordoma[J]. Med Oncol, 2013(02):529.

Froehlich, E.V., et al., Examination of survivin expression in 50 chordoma specimens--A histological and in vitro study[J]. J Orthop Res, 2015(05):771-778.

Duan, Z., et al., Differential expression of microRNA (miRNA) in chordoma reveals a role for miRNA-1 in Met expression[J]. J Orthop Res, 2010(06):746-752.

Duan, Z., et al., Prognostic significance of miRNA-1 (miR-1) expression in patients with chordoma[J]. J Orthop Res, 2014(05):695-701.

Osaka, E., et al., MicroRNA-1 (miR-1) inhibits chordoma cell migration and invasion by targeting slug[J]. J Orthop Res, 2014(08):1075-1082.

Gulluoglu, S., et al., The potential function of microRNA in chordomas[J]. Gene, 2016(01):76-83.

Bydon, M., et al., Novel therapeutic targets in chordoma[J]. Expert Opin Ther Targets, 2012(11):1139-1143.

Calin, G.A. and C.M. Croce, MicroRNA signatures in human cancers[J]. Nat Rev Cancer, 2006(11):857-866.

Bader, A.G., et al., Developing therapeutic microRNAs for cancer[J]. Gene Ther, 2011(12):1121-1126.

Zou, M.X., et al., Identification of miR-140-3p as a marker associated with poor prognosis in spinal chordoma[J]. Int J Clin Exp Pathol, 2014(08):4877-4885.

Choi, P.J., R.J. Oskouian, and R.S. Tubbs, The Current Understanding of MicroRNA’s Therapeutic, Diagnostic, and Prognostic Role in Chordomas: A Review of the Literature[J]. Cureus, 2018(12):3772.

Bayrak, O.F., et al., MicroRNA expression profiling reveals the potential function of microRNA-31 in chordomas. J Neurooncol, 2013(02):143-151.

Zou, M.X., et al., Reduced expression of miRNA-1237-3p associated with poor survival of spinal chordoma patients[J]. Eur Spine J, 2015(08):1738-1746.

Skowronski, K., et al., Genome-wide analysis in human colorectal cancer cells reveals ischemia-mediated expression of motility genes via DNA hypomethylation[J]. PLoS One, 2014(07):103243.

Rinner, B., et al., Chordoma characterization of significant changes of the DNA methylation pattern[J]. PLoS One, 2013(03):56609.

Marucci, G., et al., MGMT promoter methylation status in clival chordoma[J]. J Neurooncol, 2014(02):271-276.

Alholle, A., et al., Genome-wide DNA methylation profiling of recurrent and non-recurrent chordomas[J]. Epigenetics, 2015(03):213-220.

Scheipl, S., et al., Histone deacetylase inhibitors as potential therapeutic approaches for chordoma: an immunohistochemical and functional analysis[J]. J Orthop Res, 2013(12):1999-2005.

DOI: http://dx.doi.org/10.26549/yzlcyxzz.v3i6.5846