Citron Rho-interacting kinase silencing causes cytokinesis failure and reduces tumor growth in multiple myeloma.
Ilyas SahinYawara KawanoRomanos Sklavenitis-PistofidisMichele MoschettaYuji MishimaSalomon ManierAntonio SaccoRuben CarrascoRafael FonsecaAldo M RoccaroThomas E WitzigIrene M GhobrialPublished in: Blood advances (2020)
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.
Keyphrases
- electronic health record
- protein kinase
- gene expression
- multiple myeloma
- cell proliferation
- dna methylation
- newly diagnosed
- clinical trial
- signaling pathway
- tyrosine kinase
- poor prognosis
- machine learning
- small molecule
- cell cycle
- ejection fraction
- squamous cell carcinoma
- climate change
- genome wide
- prognostic factors
- risk assessment
- oxidative stress
- long non coding rna
- cell death
- binding protein
- mass spectrometry
- copy number
- endoplasmic reticulum stress
- artificial intelligence
- atomic force microscopy
- protein protein