Adherens junctional associated protein-1: A novel 1p36 tumor suppressor candidate in gliomas (Review)

  • Authors:
    • Liang Zeng
    • Brian E. Fee
    • Miriam V. Rivas
    • James Lin
    • David Cory Adamson
  • View Affiliations

  • Published online on: May 8, 2014     https://doi.org/10.3892/ijo.2014.2425
  • Pages: 13-17
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Abstract

In a broad range of human cancers 1p36 has been a mutational hotspot which strongly suggests that the loss of tumor suppressor activity maps to this genomic region during tumorigenesis. Adherens junctional associated protein-1 (AJAP1; also known as Shrew1) was initially discovered as a novel transmembrane protein of adherent junctions in epithelial cells. Gene profiling showed AJAP1 on 1p36 is frequently lost or epigenetically silenced. AJAP1 may affect cell motility, migration, invasion and proliferation by unclear mechanisms. AJAP1 may be translocated to the nucleus, via its interaction with β‑catenin complexes, where it can regulate gene transcription, then possibly have a potent impact on cell cycling and apoptosis. Significantly, loss of AJAP1 expression predicts poor clinical outcome of patients with malignant gliomas such as GBM and it may serve as a promising tumor suppressor-related target. In this review, we summarize and discuss current knowledge that may identify AJAP1 as a tumor suppressor in gliomas.

Contents

Introduction

Genetic and epigenetic change of AJAP1

Continuing studies on AJAP1

Relationship between AJAP1 and tumors

Closing remarks

Introduction

In a broad range of human cancers 1p36 has been a mutational hotspot, including those of nervous, secretory, reproductive and internal origin (Fig. 1) (111). These studies strongly suggest that the loss of tumor suppressor activity maps to this genomic region during tumorigenesis. The large 1p36 deletions led others to propose that more than one tumor suppressor-related gene may reside in this region (4,12). Although the quest for the 1p36 tumor suppressor has led to some exciting candidates, such as CHD5, CAMTA1, KIF1B, CASZ1 and miR-34a which have tumor suppressor-like capabilities in specific tumor contexts (1323), none can provide convincing evidence that their encoded products offer protection from cancer. Hence, the search for the 1p36 tumor suppressor continues.

Adherens junctional associated protein-1 (AJAP1; also known as Shrew1) was initially discovered as a novel trans-membrane protein of adherent junctions in epithelial cells (24). Recent investigations have suggested the AJAP1 gene as a promising tumor suppressor candidate gene located at 1p36.32 (13,24).

Genetic and epigenetic change of AJAP1

Significant data supports the role of AJAP1 loss in various tumors of the central nervous system. A single region within 1p36.3 consistently deleted in 25% of neuroblastomas was defined by White and colleagues; AJAP1 was 1 of 6 predicted genes in this deleted region (25). Neuroblastomas are neuroendocrine tumors arising from neural crest derivatives of the sympathetic nervous system (26). Fujita et al identified 23 genes, while mapping the smallest region of a consistently deleted segment of 1p36 in neuroblastomas; AJAP1 was included (27). By analyzing 430 primary neuroblastomas, Okawa et al mapped the smallest region of deletion to a 2-Mb region of 1p36 using microsatellite and single nucleotide polymorphisms and identified 23 genes in this region; including AJAP1 (13). Milde et al found the loss of AJAP1 in a progressively metastasizing ependymoma (28). Ependymomas are tumors that arise from the specialized ependyma which primarily lines the ventricular surface of the central nervous system (29). Dong et al reported two contiguous minimally deleted regions on chromosome 1p36.31-p36.32 in oligodendroglial tumors, one of which contained AJAP1 (30). Oligodendrogliomas are believed to originate from the myelin-producing oligodendrocytes of the brain (31). McDonald et al evaluated 177 oligodendroglial tumor samples and found a consensus region of deletion of approximately 630 kb. This region encompasses only one single gene - AJAP1 (32). Historically, brain gliomas have been described as likely arising from unique glial cells; however, more recent studies of genomic changes in various glioma types suggest there may be common cells of origin with common genomic changes, such as loss of AJAP1 expression.

For any tumor-suppressor activity of AJAP1 to be inhibited in a tumor, both copies of the gene must be abrogated, either by deletion or a reduction in expression. Since AJAP1 expression is found to be low in the majority of glioma tumors and cell lines (13,24,28,32,33), the remaining allele of AJAP1 has been sequenced to identify mutations, revealing none in the coding region (13,32,33). As shown for some tumor suppressors, decreased gene dosage predisposes cells to tumorigenesis. Additionally, as the expression of AJAP1 is often reduced or absent irrespective of a deletion at that locus, epigenetic silencing has been investigated. Bioinformatic analysis revealed the presence of numerous CpG islands in the promoter of AJAP1, the favored site for methylation-regulation of gene expression (33). Methylation analysis of the AJAP1 promoter identified hypermethylation in 21% of oligodendrogliomas, and the degree of methylation inversely correlated with AJAP1 expression. The AJAP1 promoter was also highly methylated in a wide spectrum of cell lines (24).

Using multiple high-resolution genomic screening methods, we found AJAP1 frequently lost or epigenetically silenced in many glioblastomas (GBM) (33). Glioblastomas which arise from astrocytes are the most common and most aggressive malignant primary brain glioma in humans which can be found throughout the brain or spinal cord (34). Expression studies revealed that loss of AJAP1 gene expression is more commonly due to epigenetic silencing of the gene than gene deletion. Expression was reduced or absent in 86–92% of primary GBM tumors (those with no history of prior lower grade tumors) and all glioma cell lines, whereas the gene was deleted in only 16% of the tumor samples. Using mutational and methylation analyses, we showed that AJAP1 expression was not due to mutation but epigenetically silenced with promoter methylation in many cases (33).

Continuing studies on AJAP1

AJAP1 was initially identified by Bharti et al in epithelial cells of the uterus as a candidate gene increased in invasive endometriosis (35). Confocal microscopic analysis of transiently-expressed AJAP1 revealed its localization at the baso-lateral part of the cell membrane, where it co-localized with endogenous E-cadherin, a protein also present at the baso-lateral part of the membrane in polarized Madin-Darby canine kidney (MDCK) epithelial cells (36,37). It has been demonstrated that adhesion is mediated by the cytoplasmic domain of E-cadherin linking to the actin cytoskeleton (38) via associated proteins such as α- and β-catenin (39). Direct interaction between β-catenin and AJAP1 in an in vitro pull-down assay suggested that AJAP1 might be directly linked to the E-cadherin via β-catenin. It can be found at the baso-lateral part of the plasma membrane where it co-localizes with, and apparently integrates into E-cadherin-mediated adherens junctions (40).

In polarized MCF7 mammary epithelial cells and MDCK cells, AJAP1 is a transmembrane protein which co-localizes with endogenous E-cadherin (35). Additionally, CD147 was shown to interact with AJAP1 and increase cell invasion (41). However, AJAP1 does not appear to interact with the N-cadherin complex in non-polarized epithelial cells (35). These findings suggest a potential role for AJAP1 in cell-cell and cell-extracellular matrix interactions that could be involved in cell motility, migration and invasion.

Apparently conflicting results are associated with AJAP1 expression. In HeLa cells (derived from a cervical tumor), loss of AJAP1 expression results in decreased invasiveness (41); however, its overexpression in glioma cells also results in decreased invasiveness, McDonald et al found in U251 cells (glioma cells) that AJAP1 overexpression decreased cell adhesion on extracellular matrix components and decreased migration in wound healing assays (32). These studies demonstrate that the effect of AJAP1 may depend on the specific cell type and its environment.

AJAP1 is an integral membrane protein of 411-amino acid residues (35) and is comprised of a cleavable N-terminal signal peptide (residues 1–43), an extracellular domain (residues 44–282), a transmembrane domain (residues 283–303) and an intracellular cytoplasmic domain (residues 304–411) (Fig. 2) (42). The relatively long signal peptide also has a role in the cellular location of AJAP1 (43,44). The signal peptide of AJAP1 conforms to the NtraC model describing the organization of long signal peptides, i.e., an N-terminal subdomain, a β-turn-rich transition area, and a C-terminal subdomain. The C-domain, either by itself or with the rest of the signal peptide, allows the targeting of nascent AJAP1 to the rough endoplasmic reticulum and subsequent transfer to the plasma membrane. The N-domain alone directs AJAP1 primarily to mitochondria. This cryptic mitochondrial targeting signal has been speculated to be active only under certain physiological conditions, e.g., apoptosis (43,44). Further analysis of the AJAP1 protein sequence revealed a putative nuclear localization signal in the predicted extracellular domain and putative glycosylation signals in the cytoplasmic domain (35).

Direct interaction between β-catenin and AJAP1 in an in vitro pull-down assay suggested that AJAP1 might be linked to the E-cadherin-mediated junctional complexes via β-catenin (35). β-catenin contains armadillo repeats and is able to bind to other proteins such as transcription factors (45). The ability of β-catenin to bind to other proteins is regulated by tyrosine kinases (46) and serine kinases such as GSK-3 (47). Various signals such as the Wnt signaling pathway can inhibit GSK-3-mediated phosphorylation of β-catenin, allowing β-catenin to translocate to the cell nucleus, interact with transcription factors, and regulate gene transcription (48). AJAP1 may be translocated to the nucleus, via its interaction with β-catenin complexes, where it can regulate gene transcription, therefore possibly having a potent impact on cell cycling and apoptosis (Fig. 3). One of our studies suggested a regulatory effect of AJAP1 on Bax/Bcl-2 ratios with increased caspase-3/7 activity in the presence of AJAP1, which indicated that AJAP1 could, at least in part, induce the mitochondria-related apoptosis pathways (49).

Relationship between AJAP1 and tumors

Cogdell and colleagues suggested overexpression of AJAP1 could suppress cell invasion and migration in GBM cell lines (24). We identified loss of AJAP1 expression as being associated with increased glioma cell proliferation and migration (33).

Interaction with β-catenin, a critical member of the Wnt signaling pathway, also suggests a possible role of AJAP1 in glioma stem cell (GSC) modulation. We observed that in the presence of AJAP1, U87MG cells (a GBM cell line) do not form tumorspheres while in the absence of AJAP1, get tumorspheres (Fig. 4). When probed for CD133, a marker of GSCs, we also noticed a decrease in its expression in AJAP1 transfected cells (data not shown) indicating either a loss of stem-like properties of the cell or decrease in the GSC subpopulation.

The group of Radlwimmer (50) performed comparative genomic hybridization and microarray analysis of spheroid cultures from GBM patients, where AJAP1 as well as EMP3 and PDPN were first described as novel candidate genes that likely play a role in GBM pathogenesis and biomarkers associated with GBM outcome. By analyzing the National Cancer Institute’s Rembrandt dataset, which contains 343 glioma samples, McDonald and colleagues (32) indicated that low AJAP1 gene expression was associated with decreased survival. Both genetic (gene deletion) and epigenetic alterations (promoter methylation) are likely mechanisms that inactivate the putative tumor suppressor AJAP1 in gliomas, which contributes to poor prognosis (24). We and others also demonstrated that the AJAP1 promoter was highly methylated in a wide spectrum of glioma cell lines, and the loss of expression was associated with poorer survival in gliomas patients (33). We recently showed that at an early stage of gliomagenesis AJAP1 is dysregulated and may suppress invasion through cytoskeleton reorganization associated with actin and microtubules associations (51). Similar result was found in a cohort study of cervical cancer (8). Restoration of AJAP1 gene expression by transfection or demethylation agents results in decreased tumor cell migration in GBM cell lines. These investigations show the significant loss of expression of AJAP1 in GBM and provide evidence of its role in the highly migratory characteristic of these tumors (33).

Closing remarks

In summary, gene profiling showed AJAP1 on 1p36 is frequently lost or epigenetically silenced in various kinds of human cancers. AJAP1 may affect cell motility, migration, invasion and proliferation by unclear mechanisms in different cell types. In particular, loss of AJAP1 expression predicts poor clinical outcome of patients with malignant gliomas such as GBM and it may serve as a promising tumor suppressor-related target. Although AJAP1 does not conform to the classical definition of a tumor suppressor, accumulating evidence from studies on other human cancers may identify AJAP1 as a tumor suppressor via the alternate dosage hypothesis.

References

1. 

Caron H, Spieker N, Godfried M, et al: Chromosome bands 1p35–36 contain two distinct neuroblastoma tumor suppressor loci, one of which is imprinted. Genes Chromosomes Cancer. 30:168–174. 2001.

2. 

Godfried MB, Veenstra M, Valent A, et al: Lack of interstitial chromosome 1p deletions in clinically-detected neuroblastoma. Eur J Cancer. 38:1513–1519. 2002. View Article : Google Scholar : PubMed/NCBI

3. 

Felsberg J, Erkwoh A, Sabel MC, et al: Oligodendroglial tumors: refinement of candidate regions on chromosome arm 1p and correlation of 1p/19q status with survival. Brain Pathol. 14:121–130. 2004. View Article : Google Scholar : PubMed/NCBI

4. 

Bagchi A, Papazoglu C, Wu Y, et al: CHD5 is a tumor suppressor at human 1p36. Cell. 128:459–475. 2007. View Article : Google Scholar : PubMed/NCBI

5. 

Piaskowski S, Rieske P, Szybka M, et al: GADD45A and EPB41 as tumor suppressor genes in meningioma pathogenesis. Cancer Genet Cytogenet. 162:63–67. 2005. View Article : Google Scholar : PubMed/NCBI

6. 

Edström Elder E, Nord B, Carling T, et al: Loss of heterozygosity on the short arm of chromosome 1 in pheochromocytoma and abdominal paraganglioma. World J Surg. 26:965–971. 2002.

7. 

Bieche I, Khodja A and Lidereau R: Deletion mapping of chromosomal region 1p32-pter in primary breast cancer. Genes Chromosomes Cancer. 24:255–263. 1999. View Article : Google Scholar

8. 

Cheung TH, Lo KW, Yim SF, et al: Clinicopathologic significance of loss of heterozygosity on chromosome 1 in cervical cancer. Gynecol Oncol. 96:510–515. 2005. View Article : Google Scholar : PubMed/NCBI

9. 

Zhou CZ, Qiu GQ, Zhang F, He L and Peng ZH: Loss of heterozygosity on chromosome 1 in sporadic colorectal carcinoma. World J Gastroenterol. 10:1431–1435. 2004.PubMed/NCBI

10. 

Girard L, Zochbauer-Muller S, Virmani AK, Gazdar AF and Minna JD: Genome-wide allelotyping of lung cancer identifies new regions of allelic loss, differences between small cell lung cancer and non-small cell lung cancer, and loci clustering. Cancer Res. 60:4894–4906. 2000.PubMed/NCBI

11. 

Kleer CG, Bryant BR, Giordano TJ, Sobel M and Merino MJ: Genetic changes in chromosomes 1p and 17p in thyroid cancer progression. Endocr Pathol. 11:137–143. 2000. View Article : Google Scholar : PubMed/NCBI

12. 

Schlisio S, Kenchappa RS, Vredeveld LC, et al: The kinesin KIF1beta acts downstream from EglN3 to induce apoptosis and is a potential 1p36 tumor suppressor. Genes Dev. 22:884–893. 2008. View Article : Google Scholar

13. 

Okawa ER, Gotoh T, Manne J, et al: Expression and sequence analysis of candidates for the 1p36.31 tumor suppressor gene deleted in neuroblastomas. Oncogene. 27:803–810. 2008. View Article : Google Scholar : PubMed/NCBI

14. 

Robbins CM, Tembe WA, Baker A, et al: Copy number and targeted mutational analysis reveals novel somatic events in metastatic prostate tumors. Genome Res. 21:47–55. 2011. View Article : Google Scholar : PubMed/NCBI

15. 

Sjoblom T, Jones S, Wood LD, et al: The consensus coding sequences of human breast and colorectal cancers. Science. 314:268–274. 2006. View Article : Google Scholar : PubMed/NCBI

16. 

Ichimura K, Vogazianou AP, Liu L, et al: 1p36 is a preferential target of chromosome 1 deletions in astrocytic tumours and homozygously deleted in a subset of glioblastomas. Oncogene. 27:2097–2108. 2008. View Article : Google Scholar : PubMed/NCBI

17. 

Tanas MR, Sboner A, Oliveira AM, et al: Identification of a disease-defining gene fusion in epithelioid hemangioendothelioma. Sci Transl Med. 3:92–98. 2011. View Article : Google Scholar : PubMed/NCBI

18. 

Henrich KO, Fischer M, Mertens D, et al: Reduced expression of CAMTA1 correlates with adverse outcome in neuroblastoma patients. Clin Cancer Res. 12:131–138. 2006. View Article : Google Scholar : PubMed/NCBI

19. 

Zhang H, Zhai Y, Hu Z, et al: Genome-wide association study identifies 1p36.22 as a new susceptibility locus for hepatocellular carcinoma in chronic hepatitis B virus carriers. Nat Genet. 42:755–758. 2010. View Article : Google Scholar : PubMed/NCBI

20. 

Caren H, Fransson S, Ejeskar K, Kogner P and Martinsson T: Genetic and epigenetic changes in the common 1p36 deletion in neuroblastoma tumours. Br J Cancer. 97:1416–1424. 2007. View Article : Google Scholar : PubMed/NCBI

21. 

Liu Z, Yang X, Li Z, et al: CASZ1, a candidate tumor-suppressor gene, suppresses neuroblastoma tumor growth through reprogramming gene expression. Cell Death Differ. 18:1174–1183. 2011. View Article : Google Scholar : PubMed/NCBI

22. 

He L, He X, Lim LP, et al: A microRNA component of the p53 tumour suppressor network. Nature. 447:1130–1134. 2007. View Article : Google Scholar

23. 

Guessous F, Zhang Y, Kofman A, et al: microRNA-34a is tumor suppressive in brain tumors and glioma stem cells. Cell Cycle. 9:1031–1036. 2010. View Article : Google Scholar

24. 

Cogdell D, Chung W, Liu Y, et al: Tumor-associated methylation of the putative tumor suppressor AJAP1 gene and association between decreased AJAP1 expression and shorter survival in patients with glioma. Chin J Cancer. 30:247–253. 2011. View Article : Google Scholar : PubMed/NCBI

25. 

White PS, Thompson PM, Gotoh T, et al: Definition and characterization of a region of 1p36.3 consistently deleted in neuroblastoma. Oncogene. 24:2684–2694. 2005. View Article : Google Scholar : PubMed/NCBI

26. 

Cheung NK and Dyer MA: Neuroblastoma: developmental biology, cancer genomics and immunotherapy. Cancer. 13:397–411. 2013.PubMed/NCBI

27. 

Fujita T, Igarashi J, Okawa ER, et al: CHD5, a tumor suppressor gene deleted from 1p36.31 in neuroblastomas. J Natl Cancer Inst. 100:940–949. 2008. View Article : Google Scholar : PubMed/NCBI

28. 

Milde T, Pfister S, Korshunov A, et al: Stepwise accumulation of distinct genomic aberrations in a patient with progressively metastasizing ependymoma. Genes Chromosomes Cancer. 48:229–238. 2009. View Article : Google Scholar : PubMed/NCBI

29. 

Nagasawa DT, Trang A, Choy W, et al: Genetic expression profiles of adult and pediatric ependymomas: molecular pathways, prognostic indicators, and therapeutic targets. Clin Neurol Neurosurg. 115:388–399. 2013. View Article : Google Scholar : PubMed/NCBI

30. 

Dong Z, Pang JS, Ng MH, Poon WS, Zhou L and Ng HK: Identification of two contiguous minimally deleted regions on chromosome 1p36.31-p36.32 in oligodendroglial tumours. Br J Cancer. 91:1105–1111. 2004. View Article : Google Scholar : PubMed/NCBI

31. 

Alentorn A, Sanson M and Idbaih A: Oligodendrogliomas: new insights from the genetics and perspectives. Curr Opin Oncol. 24:687–693. 2012. View Article : Google Scholar : PubMed/NCBI

32. 

McDonald JM, Dunlap S, Cogdell D, et al: The SHREW1 gene, frequently deleted in oligodendrogliomas, functions to inhibit cell adhesion and migration. Cancer Biol Ther. 5:300–304. 2006. View Article : Google Scholar : PubMed/NCBI

33. 

Lin N, Di C, Bortoff K, et al: Deletion or epigenetic silencing of AJAP1 on 1p36 in glioblastoma. Mol Cancer Res. 10:208–217. 2012. View Article : Google Scholar : PubMed/NCBI

34. 

Ohgaki H and Kleihues P: The definition of primary and secondary glioblastoma. Clin Cancer Res. 19:764–772. 2013. View Article : Google Scholar : PubMed/NCBI

35. 

Bharti S, Handrow-Metzmacher H, Zickenheiner S, Zeitvogel A, Baumann R and Starzinski-Powitz A: Novel membrane protein shrew-1 targets to cadherin-mediated junctions in polarized epithelial cells. Mol Biol Cell. 15:397–406. 2004. View Article : Google Scholar : PubMed/NCBI

36. 

Le Bivic A, Sambuy Y, Mostov K and Rodriguez-Boulan E: Vectorial targeting of an endogenous apical membrane sialoglyco-protein and uvomorulin in MDCK cells. J Cell Biol. 110:1533–1539. 1990.PubMed/NCBI

37. 

Shore EM and Nelson WJ: Biosynthesis of the cell adhesion molecule uvomorulin (E-cadherin) in Madin-Darby canine kidney epithelial cells. J Biol Chem. 266:19672–19680. 1991.PubMed/NCBI

38. 

Sako Y, Nagafuchi A, Tsukita S, Takeichi M and Kusumi A: Cytoplasmic regulation of the movement of E-cadherin on the free cell surface as studied by optical tweezers and single particle tracking: corralling and tethering by the membrane skeleton. J Cell Biol. 140:1227–1240. 1998. View Article : Google Scholar : PubMed/NCBI

39. 

Aberle H, Butz S, Stappert J, Weissig H, Kemler R and Hoschuetzky H: Assembly of the cadherin-catenin complex in vitro with recombinant proteins. J Cell Sci. 107:3655–3663. 1994.PubMed/NCBI

40. 

Jakob V, Schreiner A, Tikkanen R and Starzinski-Powitz A: Targeting of transmembrane protein shrew-1 to adherens junctions is controlled by cytoplasmic sorting motifs. Mol Biol Cell. 17:3397–3408. 2006. View Article : Google Scholar : PubMed/NCBI

41. 

Schreiner A, Ruonala M, Jakob V, et al: Junction protein shrew-1 influences cell invasion and interacts with invasion-promoting protein CD147. Mol Biol Cell. 18:1272–1281. 2007. View Article : Google Scholar : PubMed/NCBI

42. 

Resch E, Quaiser S, Quaiser T, Schneider G, Starzinski-Powitz A and Schreiner A: Synergism of shrew-1’s signal peptide and transmembrane segment required for plasma membrane localization. Traffic. 9:1344–1353. 2008.PubMed/NCBI

43. 

Hiss JA, Resch E, Schreiner A, Meissner M, Starzinski-Powitz A and Schneider G: Domain organization of long signal peptides of single-pass integral membrane proteins reveals multiple functional capacity. PloS One. 3:e27672008. View Article : Google Scholar : PubMed/NCBI

44. 

Resch E, Hiss JA, Schreiner A, Schneider G and Starzinski-Powitz A: Long signal peptides of RGMa and DCBLD2 are dissectible into subdomains according to the NtraC model. Mol Biosyst. 7:942–951. 2011. View Article : Google Scholar : PubMed/NCBI

45. 

Gottardi CJ and Peifer M: Terminal regions of beta-catenin come into view. Structure. 16:336–338. 2008. View Article : Google Scholar : PubMed/NCBI

46. 

Lilien J and Balsamo J: The regulation of cadherin-mediated adhesion by tyrosine phosphorylation/dephosphorylation of beta-catenin. Curr Opin Cell Biol. 17:459–465. 2005. View Article : Google Scholar : PubMed/NCBI

47. 

Castellone MD, Teramoto H, Williams BO, Druey KM and Gutkind JS: Prostaglandin E2 promotes colon cancer cell growth through a Gs-axin-beta-catenin signaling axis. Science. 310:1504–1510. 2005. View Article : Google Scholar : PubMed/NCBI

48. 

Liu X, Rubin JS and Kimmel AR: Rapid, Wnt-induced changes in GSK3beta associations that regulate beta-catenin stabilization are mediated by Galpha proteins. Curr Biol. 15:1989–1997. 2005. View Article : Google Scholar : PubMed/NCBI

49. 

Zeng L, Kang C, Di C, et al: The adherens junction-associated protein 1 is a negative transcriptional regulator of MAGEA2, which potentiates temozolomide-induced apoptosis in GBM. Int J Oncol. 44:1243–1251. 2014.

50. 

Ernst A, Hofmann S, Ahmadi R, et al: Genomic and expression profiling of glioblastoma stem cell-like spheroid cultures identifies novel tumor-relevant genes associated with survival. Clin Cancer Res. 15:6541–6550. 2009. View Article : Google Scholar

51. 

Han L, Zhang KL, Zhang JX, et al: AJAP1 is dysregulated at an early stage of gliomagenesis and suppresses invasion through cytoskeleton re-organization. CNS Neurosci Ther. 20:429–437. 2014. View Article : Google Scholar : PubMed/NCBI

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Zeng L, Fee BE, Rivas MV, Lin J and Adamson DC: Adherens junctional associated protein-1: A novel 1p36 tumor suppressor candidate in gliomas (Review). Int J Oncol 45: 13-17, 2014
APA
Zeng, L., Fee, B.E., Rivas, M.V., Lin, J., & Adamson, D.C. (2014). Adherens junctional associated protein-1: A novel 1p36 tumor suppressor candidate in gliomas (Review). International Journal of Oncology, 45, 13-17. https://doi.org/10.3892/ijo.2014.2425
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Zeng, L., Fee, B. E., Rivas, M. V., Lin, J., Adamson, D. C."Adherens junctional associated protein-1: A novel 1p36 tumor suppressor candidate in gliomas (Review)". International Journal of Oncology 45.1 (2014): 13-17.
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Zeng, L., Fee, B. E., Rivas, M. V., Lin, J., Adamson, D. C."Adherens junctional associated protein-1: A novel 1p36 tumor suppressor candidate in gliomas (Review)". International Journal of Oncology 45, no. 1 (2014): 13-17. https://doi.org/10.3892/ijo.2014.2425