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Article

Disabled Homolog 2 (DAB2) Protein in Tumor Microenvironment Correlates with Aggressive Phenotype in Human Urothelial Carcinoma of the Bladder

1
Department of Urology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8522, Japan
2
Department of Pathology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8522, Japan
3
Department of Pathology, Nara City Hospital, 1-50-1 Higashi kidera-cho, Nara 630-8305, Japan
4
Division of Urology, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
5
Bioinformatics Core, Department of Complementary and Integrative Medicine, University of Hawaii John A. Burns School of Medicine, Honolulu, HI 96813, USA
*
Author to whom correspondence should be addressed.
Diagnostics 2020, 10(1), 54; https://doi.org/10.3390/diagnostics10010054
Received: 25 December 2019 / Revised: 14 January 2020 / Accepted: 17 January 2020 / Published: 20 January 2020
(This article belongs to the Special Issue Urogenital Cancers: Diagnostic, Predictive, and Prognostic Markers)
Disabled homolog-2 (DAB2) has been reported to be a tumor suppressor gene. However, a number of contrary studies suggested that DAB2 promotes tumor invasion in urothelial carcinoma of the bladder (UCB). Here, we investigated the clinical role and biological function of DAB2 in human UCB. Immunohistochemical staining analysis for DAB2 was carried out on UCB tissue specimens. DAB2 expression levels were compared with clinicopathological factors. DAB2 was knocked-down by small interfering RNA (siRNA) transfection, and then its effects on cell proliferation, invasion, and migration, and changes to epithelial-mesenchymal transition (EMT)-related proteins were evaluated. In our in vivo assays, tumor-bearing athymic nude mice subcutaneously inoculated with human UCB cells (MGH-U-3 or UM-UC-3) were treated by DAB2-targeting siRNA. Higher expression of DAB2 was associated with higher clinical T category, high tumor grade, and poor oncological outcome. The knock-down of DAB2 decreased both invasion and migration ability and expression of EMT-related proteins. Significant inhibitory effects on tumor growth and invasion were observed in xenograft tumors of UM-UC-3 treated by DAB2-targeting siRNA. Our findings suggested that DAB2 expression was associated with poor prognosis through increased oncogenic properties including tumor proliferation, migration, invasion, and enhancement of EMT in human UCB. View Full-Text
Keywords: DAB2; bladder cancer; epithelial-mesenchymal transition DAB2; bladder cancer; epithelial-mesenchymal transition
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MDPI and ACS Style

Itami, Y.; Miyake, M.; Ohnishi, S.; Tatsumi, Y.; Gotoh, D.; Hori, S.; Morizawa, Y.; Iida, K.; Ohnishi, K.; Nakai, Y.; Inoue, T.; Anai, S.; Tanaka, N.; Fujii, T.; Shimada, K.; Furuya, H.; Khadka, V.S.; Deng, Y.; Fujimoto, K. Disabled Homolog 2 (DAB2) Protein in Tumor Microenvironment Correlates with Aggressive Phenotype in Human Urothelial Carcinoma of the Bladder. Diagnostics 2020, 10, 54. https://doi.org/10.3390/diagnostics10010054

AMA Style

Itami Y, Miyake M, Ohnishi S, Tatsumi Y, Gotoh D, Hori S, Morizawa Y, Iida K, Ohnishi K, Nakai Y, Inoue T, Anai S, Tanaka N, Fujii T, Shimada K, Furuya H, Khadka VS, Deng Y, Fujimoto K. Disabled Homolog 2 (DAB2) Protein in Tumor Microenvironment Correlates with Aggressive Phenotype in Human Urothelial Carcinoma of the Bladder. Diagnostics. 2020; 10(1):54. https://doi.org/10.3390/diagnostics10010054

Chicago/Turabian Style

Itami, Yoshitaka, Makito Miyake, Sayuri Ohnishi, Yoshihiro Tatsumi, Daisuke Gotoh, Shunta Hori, Yousuke Morizawa, Kota Iida, Kenta Ohnishi, Yasushi Nakai, Takeshi Inoue, Satoshi Anai, Nobumichi Tanaka, Tomomi Fujii, Keiji Shimada, Hideki Furuya, Vedbar S. Khadka, Youping Deng, and Kiyohide Fujimoto. 2020. "Disabled Homolog 2 (DAB2) Protein in Tumor Microenvironment Correlates with Aggressive Phenotype in Human Urothelial Carcinoma of the Bladder" Diagnostics 10, no. 1: 54. https://doi.org/10.3390/diagnostics10010054

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