J Cancer 2023; 14(5):689-706. doi:10.7150/jca.79552 This issue Cite

Research Paper

Inhibition of PANX1 Channels Reduces the Malignant Properties of Human High-Risk Neuroblastoma

Stéphanie Langlois1,3*, Marie-Eve St-Pierre1*, Stephen H. Holland1,2, Xiao Xiang1,2, Emily Freeman1,2, Hisham Mohamed3, Ahmet Cem Dural1,3, Ahmed Hammad1,3, Sanaz Karami1, Chloé van de Panne1, Kyle N. Cowan1,2,3✉

1. Molecular Biomedicine Program, Children's Hospital of Eastern Ontario Research Institute, Ottawa, Ontario, Canada
2. Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario, Canada
3. Department of Surgery, Children's Hospital of Eastern Ontario, University of Ottawa, Ottawa, Ontario, Canada
*These authors contributed equally to this work.

Citation:
Langlois S, St-Pierre ME, Holland SH, Xiang X, Freeman E, Mohamed H, Dural AC, Hammad A, Karami S, van de Panne C, Cowan KN. Inhibition of PANX1 Channels Reduces the Malignant Properties of Human High-Risk Neuroblastoma. J Cancer 2023; 14(5):689-706. doi:10.7150/jca.79552. https://www.jcancer.org/v14p0689.htm
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Abstract

Graphic abstract

Pannexin 1 (PANX1) is expressed in many tissue types including tissues of neural origin. Neuroblastoma (NB) is a neural crest-derived malignancy mainly occurring in children. The majority of NB patients present with high-risk disease for which current therapies are ineffective. Here, we show that while PANX1 is expressed in NB of all stages, high PANX1 expression in high-risk NB is associated with a reduced survival probability. PANX1 channel inhibition using probenecid (PBN) or carbenoxolone (CBX) reduced the proliferation of our panel of high-risk NB cell lines. We show that expression of the Y10F PANX1 mutant, which cannot be phosphorylated on tyrosine 10 and acts in a dominant-negative manner, curtailed NB cell proliferation. Furthermore, PBN and CBX treatment halted the growth of NB spheroids and in some cases triggered the regression of established NB spheroids. Finally, both drugs reduced the progression of high-risk NB in vivo. Together our data indicate that PANX1 channels regulate human NB malignant properties and that the use of PBN or CBX may provide a new therapeutic approach for high-risk NB.

Keywords: Cancer, Carbenoxolone, Neuroblastoma, Pannexin, PANX1, Probenecid, Xenografts


Citation styles

APA
Langlois, S., St-Pierre, M.E., Holland, S.H., Xiang, X., Freeman, E., Mohamed, H., Dural, A.C., Hammad, A., Karami, S., van de Panne, C., Cowan, K.N. (2023). Inhibition of PANX1 Channels Reduces the Malignant Properties of Human High-Risk Neuroblastoma. Journal of Cancer, 14(5), 689-706. https://doi.org/10.7150/jca.79552.

ACS
Langlois, S.; St-Pierre, M.E.; Holland, S.H.; Xiang, X.; Freeman, E.; Mohamed, H.; Dural, A.C.; Hammad, A.; Karami, S.; van de Panne, C.; Cowan, K.N. Inhibition of PANX1 Channels Reduces the Malignant Properties of Human High-Risk Neuroblastoma. J. Cancer 2023, 14 (5), 689-706. DOI: 10.7150/jca.79552.

NLM
Langlois S, St-Pierre ME, Holland SH, Xiang X, Freeman E, Mohamed H, Dural AC, Hammad A, Karami S, van de Panne C, Cowan KN. Inhibition of PANX1 Channels Reduces the Malignant Properties of Human High-Risk Neuroblastoma. J Cancer 2023; 14(5):689-706. doi:10.7150/jca.79552. https://www.jcancer.org/v14p0689.htm

CSE
Langlois S, St-Pierre ME, Holland SH, Xiang X, Freeman E, Mohamed H, Dural AC, Hammad A, Karami S, van de Panne C, Cowan KN. 2023. Inhibition of PANX1 Channels Reduces the Malignant Properties of Human High-Risk Neuroblastoma. J Cancer. 14(5):689-706.

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