Research Papers:

Identification of α-N-catenin as a novel tumor suppressor in neuroblastoma

Jingbo Qiao, Eric J. Rellinger, Kwang Woon Kim, Camille M. Powers, Sora Lee, Hernan Correa and Dai H. Chung

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Oncotarget. 2019; 10:5028-5040. https://doi.org/10.18632/oncotarget.27096

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Jingbo Qiao1,*, Eric J. Rellinger2,*, Kwang Woon Kim1, Camille M. Powers2, Sora Lee1, Hernan Correa3 and Dai H. Chung1

1 Department of Surgery, UT Southwestern Medical Center, Dallas, TX 75390, USA

2 Department of Pediatric Surgery, Vanderbilt University Medical Center, Nashville, TN 37232, USA

3 Department of Pathology, Vanderbilt University Medical Center, Nashville, TN 37232, USA

* These authors contributed equally to this work

Correspondence to:

Dai H. Chung,email: [email protected]

Keywords: neuroblastoma; tumor suppressor; CTNNA2 (α-N-catenin); NF-κB

Received: March 25, 2019     Accepted: June 14, 2019     Published: August 20, 2019


The lost expression of α-catenin has been found in cancers, and reinstalling α-catenin inhibits tumor growth. Here we hypothesized that the α-N-catenin, a homologous member of α-catenin and neural-specific expressed, functions as a novel tumor suppressor in neural crest-derived tumor, neuroblastoma. We correlated CTNNA2 (encodes α-N-catenin) expression to neuroblastoma disease relapse-free survival probability using publicly accessible human neuroblastoma datasets in R2 platform. The result showed that it negatively correlated to relapse-free survival probability significantly in patients with neuroblastoma with non-MYCN amplified tumor. Conversely, overexpressing CTNNA2 suppressed the neuroblastoma cell proliferation as measuring by the clonogenesis, inhibited anchorage-independent growth with soft agar colony formation assay. Forced expression of CTNNA2 decreased cell migration and invasion. Further, overexpression of CTNNA2 reduced the secretion of angiogenic factor IL-8 and HUVEC tubule formation. Our results show, for the first time, that α-N-catenin is a tumor suppressor in neuroblastoma cells. These findings were further corroborated with in vivo tumor xenograft study, in which α-N-catenin inhibited tumor growth and reduced tumor blood vessel formation. Interestingly, this is only observed in SK-N-AS xenografts lacking MYCN expression, and not in BE(2)-C xenografts with MYCN amplification. Mechanistically, α-N-catenin attenuated NF-κB responsive genes by inhibiting NF-κB transcriptional activity. In conclusion, these data demonstrate that α-N-catenin is a tumor suppressor in non-MYCN-amplified neuroblastomas and it inhibits NF-κB signaling pathway to suppress tumor growth in human neuroblastomas. Therefore, restoring the expression of α-N-catenin can be a novel therapeutic approach for neuroblastoma patients who have the deletion of CTNNA2 and lack of MYCN amplification.

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