Journal Article

Silencing of I<i>k</i>Bβ mRNA causes disruption of mitochondrial retrograde signaling and suppression of tumor growth <i>in vivo</i>

Weigang Tang, Anindya Roy Chowdhury, Manti Guha, Li Huang, Thomas Van Winkle, Anil K. Rustgi and Narayan G. Avadhani

in Carcinogenesis

Volume 33, issue 9, pages 1762-1768
Published in print September 2012 | ISSN: 0143-3334
Published online May 2012 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgs190
Silencing of IkBβ mRNA causes disruption of mitochondrial retrograde signaling and suppression of tumor growth in vivo

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A number of studies show that mitochondrial DNA (mtDNA) depletion and attendant activation of retrograde signaling induces tumor progression. We have reported previously that activation of a novel nuclear factor-Kappa B pathway is critical for the propagation of mitochondrial retrograde signaling, which induces both phenotypic and morphological changes in C2C12 myoblasts and A549 lung carcinoma cells. In this study, we investigated the role of stress-induced nuclear factor-Kappa B in tumor progression in xenotransplanted mice. We used a retroviral system for the inducible expression of small interfering RNA against IkBα and IkBβ mRNAs. Expression of small interfering RNA against IkBβ markedly impaired tumor growth and invasive ability of mtDNA-depleted C2C12 myoblasts and also thwarted anchorage-independent growth of the cells. Knockdown of IkBα mRNA, however, did not have any modulatory effect in this cell system. Moreover, expression of small interfering RNA against IkBβ reduced the expression of marker genes for retrograde signaling and tumor growth in xenografts of mtDNA-depleted cells. Our findings demonstrate that IkBβ is a master regulator of mitochondrial retrograde signaling pathway and that the retrograde signaling plays a role in tumor growth in vivo. In this regard, IkBβ supports the tumorigenic potential of mtDNA-depleted C2C12 cells.

Journal Article.  5935 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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