Citron Rho-interacting kinase silencing causes cytokinesis failure and reduces tumor growth in multiple myeloma

Ilyas Sahin, Yawara Kawano, Romanos Sklavenitis-Pistofidis, Michele Moschetta, Yuji Mishima, Salomon Manier, Antonio Sacco, Ruben Carrasco, Rafael Fonseca, Aldo M. Roccaro, Thomas Elmer Witzig, Irene M. Ghobrial

Research output: Contribution to journalArticle

Abstract

Citron Rho-interacting serine/threonine kinase (CIT) is a serine/threonine kinase that acts as a key component of the midbody and is essential for cytokinesis. CIT has been reported to be highly expressed in some tumor tissues and to play a role in cancer proliferation; however, the significance of CIT has not been investigated in multiple myeloma (MM). Here, we identified, by protein microarray and immunohistochemistry, that CIT is 1 of the upregulated proteins in the plasma cells of MM patients compared with healthy controls. Analysis of a gene expression profile data set showed that MM patients with high CIT gene expression had significantly worse overall survival compared with MM patients with low CIT gene expression. CIT silencing in MM cell lines induced cytokinesis failure and resulted in decreased MM cell proliferation in vitro and in vivo. TP53 expression was found to be an independent predictor of CIT dependency, with low-TP53 cell lines exhibiting a strong dependency on CIT. This study provides the rationale for CIT being a potential therapeutic target in MM in future trials.

Original languageEnglish (US)
Pages (from-to)995-1002
Number of pages8
JournalBlood Advances
Volume3
Issue number7
DOIs
StatePublished - Apr 9 2019

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Cytokinesis
Multiple Myeloma
Growth
Neoplasms
Protein-Serine-Threonine Kinases
Gene Expression
Cell Line
Protein Array Analysis
citron-kinase
Transcriptome
Immunohistochemistry
Cell Proliferation
Survival

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Sahin, I., Kawano, Y., Sklavenitis-Pistofidis, R., Moschetta, M., Mishima, Y., Manier, S., ... Ghobrial, I. M. (2019). Citron Rho-interacting kinase silencing causes cytokinesis failure and reduces tumor growth in multiple myeloma. Blood Advances, 3(7), 995-1002. https://doi.org/10.1182/bloodadvances.2018028456

Citron Rho-interacting kinase silencing causes cytokinesis failure and reduces tumor growth in multiple myeloma. / Sahin, Ilyas; Kawano, Yawara; Sklavenitis-Pistofidis, Romanos; Moschetta, Michele; Mishima, Yuji; Manier, Salomon; Sacco, Antonio; Carrasco, Ruben; Fonseca, Rafael; Roccaro, Aldo M.; Witzig, Thomas Elmer; Ghobrial, Irene M.

In: Blood Advances, Vol. 3, No. 7, 09.04.2019, p. 995-1002.

Research output: Contribution to journalArticle

Sahin, I, Kawano, Y, Sklavenitis-Pistofidis, R, Moschetta, M, Mishima, Y, Manier, S, Sacco, A, Carrasco, R, Fonseca, R, Roccaro, AM, Witzig, TE & Ghobrial, IM 2019, 'Citron Rho-interacting kinase silencing causes cytokinesis failure and reduces tumor growth in multiple myeloma', Blood Advances, vol. 3, no. 7, pp. 995-1002. https://doi.org/10.1182/bloodadvances.2018028456
Sahin, Ilyas ; Kawano, Yawara ; Sklavenitis-Pistofidis, Romanos ; Moschetta, Michele ; Mishima, Yuji ; Manier, Salomon ; Sacco, Antonio ; Carrasco, Ruben ; Fonseca, Rafael ; Roccaro, Aldo M. ; Witzig, Thomas Elmer ; Ghobrial, Irene M. / Citron Rho-interacting kinase silencing causes cytokinesis failure and reduces tumor growth in multiple myeloma. In: Blood Advances. 2019 ; Vol. 3, No. 7. pp. 995-1002.
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