Microtubule actin cross-linking factor 1, a novel target in glioblastoma

Afghani,Najlaa; Mehta,Toral; Wang,Jialiang; Tang,Nan; Skalli,Omar; Quick,Quincy A.

doi:10.3892/ijo.2016.3798

Microtubule actin cross-linking factor 1, a novel target in glioblastoma

Authors:
- Najlaa Afghani
- Toral Mehta
- Jialiang Wang
- Nan Tang
- Omar Skalli
- Quincy A. Quick
View Affiliations

Affiliations: Department of Biological Sciences, Tennessee State University, Nashville, TN, USA, Department of Neurological Surgery, Vanderbilt Medical Center, Nashville, TN, USA, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, P.R. China, Department of Biological Sciences, University of Memphis, Memphis, TN, USA
Published online on: December 9, 2016 https://doi.org/10.3892/ijo.2016.3798
Pages: 310-316

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Genetic heterogeneity is recognized as a major contributing factor of glioblastoma resistance to clinical treatment modalities and consequently low overall survival rates. This genetic diversity results in variations in protein expression, both intratumorally and between individual glioblastoma patients. In this regard, the spectraplakin protein, microtubule actin cross-linking factor 1 (MACF1), was examined in glioblastoma. An expression analysis of MACF1 in various types of brain tumor tissue revealed that MACF1 was predominately present in grade III-IV astroctyomas and grade IV glioblastoma, but not in normal brain tissue, normal human astrocytes and lower grade brain tumors. Subsequent genetic inhibition experiments showed that suppression of MACF1 selectively inhibited glioblastoma cell proliferation and migration in cell lines established from patient derived xenograft mouse models and immortalized glioblastoma cell lines that were associated with downregulation of the Wnt-signaling mediators, Axin1 and β-catenin. Additionally, concomitant MACF1 silencing with the chemotherapeutic agent temozolomide (TMZ) used for the clinical treatment of glioblastomas cooperatively reduced the proliferative capacity of glioblastoma cells. In conclusion, the present study represents the first investigation on the functional role of MACF1 in tumor cell biology, as well as demonstrates its potential as a unique biomarker that can be targeted synergistically with TMZ as part of a combinatorial therapeutic approach for the treatment of genetically multifarious glioblastomas.

View Figures

View References

1	Ostrom QT, Bauchet L, Davis FG, Deltour I, Fisher JL, Langer CE, Pekmezci M, Schwartzbaum JA, Turner MC, Walsh KM, et al: The epidemiology of glioma in adults: A 'state of the science' review. Neuro Oncol. 16:896–913. 2014. View Article : Google Scholar : PubMed/NCBI
2	Reardon DA and Wen PY: Glioma in 2014: Unravelling tumour heterogeneity - implications for therapy. Nat Rev Clin Oncol. 12:69–70. 2015. View Article : Google Scholar : PubMed/NCBI
3	Parsons DW, Jones S, Zhang X, Lin JC, Leary RJ, Angenendt P, Mankoo P, Carter H, Siu IM, Gallia GL, et al: An integrated genomic analysis of human glioblastoma multiforme. Science. 321:1807–1812. 2008. View Article : Google Scholar : PubMed/NCBI
4	Verhaak RG, Hoadley KA, Purdom E, Wang V, Qi Y, Wilkerson MD, Miller CR, Ding L, Golub T, Mesirov JP, et al Cancer Genome Atlas Research Network: Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1. Cancer Cell. 17:98–110. 2010. View Article : Google Scholar : PubMed/NCBI
5	Heimberger AB, Hlatky R, Suki D, Yang D, Weinberg J, Gilbert M, Sawaya R and Aldape K: Prognostic effect of epidermal growth factor receptor and EGFRvIII in glioblastoma multiforme patients. Clin Cancer Res. 11:1462–1466. 2005. View Article : Google Scholar : PubMed/NCBI
6	Pelloski CE, Ballman KV, Furth AF, Zhang L, Lin E, Sulman EP, Bhat K, McDonald JM, Yung WK, Colman H, et al: Epidermal growth factor receptor variant III status defines clinically distinct subtypes of glioblastoma. J Clin Oncol. 25:2288–2294. 2007. View Article : Google Scholar : PubMed/NCBI
7	Hegi ME, Diserens AC, Gorlia T, Hamou MF, de Tribolet N, Weller M, Kros JM, Hainfellner JA, Mason W, Mariani L, et al: MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med. 352:997–1003. 2005. View Article : Google Scholar : PubMed/NCBI
8	Rivera AL, Pelloski CE, Gilbert MR, Colman H, De La Cruz C, Sulman EP, Bekele BN and Aldape KD: MGMT promoter methylation is predictive of response to radiotherapy and prognostic in the absence of adjuvant alkylating chemotherapy for glioblastoma. Neuro Oncol. 12:116–121. 2010. View Article : Google Scholar : PubMed/NCBI
9	Sanchez-Soriano N, Travis M, Dajas-Bailador F, Gonçalves-Pimentel C, Whitmarsh AJ and Prokop A: Mouse ACF7 and drosophila short stop modulate filopodia formation and microtubule organisation during neuronal growth. J Cell Sci. 122:2534–2542. 2009. View Article : Google Scholar : PubMed/NCBI
10	Munemasa Y, Chang CS, Kwong JM, Kyung H, Kitaoka Y, Caprioli J and Piri N: The neuronal EGF-related gene Nell2 interacts with Macf1 and supports survival of retinal ganglion cells after optic nerve injury. PLoS One. 7:e348102012. View Article : Google Scholar : PubMed/NCBI
11	Bernier G, Pool M, Kilcup M, Alfoldi J, De Repentigny Y and Kothary R: Acf7 (MACF) is an actin and microtubule linker protein whose expression predominates in neural, muscle, and lung development. Dev Dyn. 219:216–225. 2000. View Article : Google Scholar : PubMed/NCBI
12	Sjöblom T, Jones S, Wood LD, Parsons DW, Lin J, Barber TD, Mandelker D, Leary RJ, Ptak J, Silliman N, et al: The consensus coding sequences of human breast and colorectal cancers. Science. 314:268–274. 2006. View Article : Google Scholar : PubMed/NCBI
13	Misquitta-Ali CM, Cheng E, O'Hanlon D, Liu N, McGlade CJ, Tsao MS and Blencowe BJ: Global profiling and molecular characterization of alternative splicing events misregulated in lung cancer. Mol Cell Biol. 31:138–150. 2011. View Article : Google Scholar :
14	Carlson BL, Pokorny JL, Schroeder MA and Sarkaria JN: Establishment, maintenance and in vitro and in vivo applications of primary human glioblastoma multiforme (GBM) xenograft models for translational biology studies and drug discovery. Curr Protoc Pharmacol Chapter. 14:162011.
15	Chiba K, Kawakami K and Tohyama K: Simultaneous evaluation of cell viability by neutral red, MTT and crystal violet staining assays of the same cells. Toxicol In Vitro. 12:251–258. 1998. View Article : Google Scholar : PubMed/NCBI
16	Chen HJ, Lin CM, Lin CS, Perez-Olle R, Leung CL and Liem RK: The role of microtubule actin cross-linking factor 1 (MACF1) in the Wnt signaling pathway. Genes Dev. 20:1933–1945. 2006. View Article : Google Scholar : PubMed/NCBI
17	Wu X, Shen QT, Oristian DS, Lu CP, Zheng Q, Wang HW and Fuchs E: Skin stem cells orchestrate directional migration by regulating microtubule-ACF7 connections through GSK3β. Cell. 144:341–352. 2011. View Article : Google Scholar : PubMed/NCBI
18	Yin X, Xiang T, Li L, Su X, Shu X, Luo X, Huang J, Yuan Y, Peng W, Oberst M, et al: DACT1, an antagonist to Wnt/β-catenin signaling, suppresses tumor cell growth and is frequently silenced in breast cancer. Breast Cancer Res. 15:R232013. View Article : Google Scholar
19	Narayanan BA, Doudican NA, Park J, Xu D, Narayanan NK, Dasgupta R and Mazumder A: Antagonistic effect of small-molecule inhibitors of Wnt/β-catenin in multiple myeloma. Anticancer Res. 32:4697–4707. 2012.PubMed/NCBI
20	Bakker ER, Das AM, Helvensteijn W, Franken PF, Swagemakers S, van der Valk MA, ten Hagen TL, Kuipers EJ, van Veelen W and Smits R: Wnt5a promotes human colon cancer cell migration and invasion but does not augment intestinal tumorigenesis in Apc1638N mice. Carcinogenesis. 34:2629–2638. 2013. View Article : Google Scholar : PubMed/NCBI
21	Yu JM, Jun ES and Jung JS, Suh SY, Han JY, Kim JY, Kim KW and Jung JS: Role of Wnt5a in the proliferation of human glioblastoma cells. Cancer Lett. 257:172–181. 2007. View Article : Google Scholar : PubMed/NCBI
22	Pu P, Zhang Z, Kang C, Jiang R, Jia Z, Wang G and Jiang H: Downregulation of Wnt2 and beta-catenin by siRNA suppresses malignant glioma cell growth. Cancer Gene Ther. 16:351–361. 2009. View Article : Google Scholar
23	De Robertis A, Valensin S, Rossi M, Tunici P, Verani M, De Rosa A, Giordano C, Varrone M, Nencini A, Pratelli C, et al: Identification and characterization of a small-molecule inhibitor of Wnt signaling in glioblastoma cells. Mol Cancer Ther. 12:1180–1189. 2013. View Article : Google Scholar : PubMed/NCBI
24	Kaur N, Chettiar S, Rathod S, Rath P, Muzumdar D, Shaikh ML and Shiras A: Wnt3a mediated activation of Wnt/β-catenin signaling promotes tumor progression in glioblastoma. Mol Cell Neurosci. 54:44–57. 2013. View Article : Google Scholar : PubMed/NCBI
25	Ramirez YP, Weatherbee JL, Wheelhouse RT and Ross AH: Glioblastoma multiforme therapy and mechanisms of resistance. Pharmaceuticals (Basel). 6:1475–1506. 2013. View Article : Google Scholar
26	Clark MJ, Homer N, O'Connor BD, Chen Z, Eskin A, Lee H, Merriman B and Nelson SF: U87MG decoded: The genomic sequence of a cytogenetically aberrant human cancer cell line. PLoS Genet. 6:e10008322010. View Article : Google Scholar : PubMed/NCBI
27	Quick Q, Paul M and Skalli O: Roles and potential clinical applications of intermediate filament proteins in brain tumors. Semin Pediatr Neurol. 22:40–48. 2015. View Article : Google Scholar : PubMed/NCBI
28	Hu L, Su P, Li R, Yan K, Chen Z, Shang P and Qian A: Knockdown of microtubule actin crosslinking factor 1 inhibits cell proliferation in MC3T3-E1 osteoblastic cells. BMB Rep. 48:583–588. 2015. View Article : Google Scholar : PubMed/NCBI
29	Ishii N, Maier D, Merlo A, Tada M, Sawamura Y, Diserens AC and Van Meir EG: Frequent co-alterations of TP53, p16/CDKN2A, p14^ARF, PTEN tumor suppressor genes in human glioma cell lines. Brain Pathol. 9:469–479. 1999. View Article : Google Scholar : PubMed/NCBI
30	Hu L, Su P, Li R, Yin C, Zhang Y, Shang P, Yang T and Qian A: MACF1, a versatile spectraplakin: Isoforms, unique structures, and functions. BMB Rep. 49:37–44. 2016. View Article : Google Scholar :
31	Quick Q and Skalli O: Alpha-actinin 1 and alpha-actinin 4: Contrasting roles in the survival, motility, and RhoA signaling of astrocytoma cells. Exp Cell Res. 316:1137–1147. 2010. View Article : Google Scholar : PubMed/NCBI
32	von Neubeck C, Seidlitz A, Kitzler HH, Beuthien-Baumann B and Krause M: Glioblastoma multiforme: Emerging treatments and stratification markers beyond new drugs. Br J Radiol. 88:201503542015. View Article : Google Scholar : PubMed/NCBI
33	Loftus JC, Dhruv H, Tuncali S, Kloss J, Yang Z, Schumacher CA, Cao B, Williams BO, Eschbacher JM, Ross JT, et al: TROY (TNFRSF19) promotes glioblastoma survival signaling and therapeutic resistance. Mol Cancer Res. 11:865–874. 2013. View Article : Google Scholar : PubMed/NCBI
34	Choi EJ, Cho BJ, Lee DJ, Hwang YH, Chun SH, Kim HH and Kim IA: Enhanced cytotoxic effect of radiation and temozolomide in malignant glioma cells: Targeting PI3K-AKT-mTOR signaling, HSP90 and histone deacetylases. BMC Cancer. 14:172014. View Article : Google Scholar : PubMed/NCBI
35	Vo VA, Lee JW, Lee HJ, Chun W, Lim SY and Kim SS: Inhibition of JNK potentiates temozolomide-induced cytotoxicity in U87MG glioblastoma cells via suppression of Akt phosphorylation. Anticancer Res. 34:5509–5515. 2014.PubMed/NCBI
36	Hainsworth JD, Shih KC, Shepard GC, Tillinghast GW, Brinker BT and Spigel DR: Phase II study of concurrent radiation therapy, temozolomide, and bevacizumab followed by bevacizumab/everolimus as first-line treatment for patients with glioblastoma. Clin Adv Hematol Oncol. 10:240–246. 2012.PubMed/NCBI
37	Chinot OL, Wick W, Mason W, Henriksson R, Saran F, Nishikawa R, Carpentier AF, Hoang-Xuan K, Kavan P, Cernea D, et al: Bevacizumab plus radiotherapy-temozolomide for newly diagnosed glioblastoma. N Engl J Med. 370:709–722. 2014. View Article : Google Scholar : PubMed/NCBI
38	Clarke JL, Molinaro AM, Phillips JJ, Butowski NA, Chang SM, Perry A, Costello JF, DeSilva AA, Rabbitt JE and Prados MD: A single-institution phase II trial of radiation, temozolomide, erlotinib, and bevacizumab for initial treatment of glioblastoma. Neuro Oncol. 16:984–990. 2014. View Article : Google Scholar : PubMed/NCBI