NFAT/SIRT3 mediated regulation of metabolic adaptation driving prostate cancer bone metastasis 

In this prostate cancer-focused project, we propose that prostate cancer cells adapt to the environmental stresses in the bone milieu in a non-conventional way and gain the capacity to convert nutrition to energy and basic cellular building blocks, namely, metabolic adaptation. 

We hypothesize that this process is double-regulated by the hyper-activation of organ-specific, oncogenic NFAT (nuclear factor of activated T cells) signaling in combination with the suppression of metabolic repressor Sirtuin 3 (SIRT3). 

Figure from a scientific research study

Our early work disclosed an unexpected role for SIRT3 in the regulation of NFAT levels. Additionally, our studies, for the first time, have identified a collaborative and mutually interfering regulatory cascade as a critical mechanism that supports the metabolic adaptation and metastatic progression of prostate cancer cells in bone metastasis, thereby allowing cancer cells to survive amidst a limited nutrition supply and environmental stresses in the bone milieu. 

The involvement of the indicated genes was supported by public genomics data and pilot biological studies. These findings provide a compelling rationale to investigate and target the indicated metabolic axis for bone metastases. 

See the science

Cover of Cancer Cell Journal

The osteogenic niche is a calcium reservoir of bone micrometastases and confers unexpected therapeutic vulnerability

  • Journal: Cancer Cell, November 2018
  • Authors: Hai Wang, et al.
  • Citation: Cancer Cell. 2018 Nov 12; 34(5): 823–839.e7. doi: 10.1016/j.ccell.2018.10.002
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Contact the Wang Lab

Lab Location: Medical Research Complex - Room 358  

Department of Molecular and Cellular Biology
Roswell Park Comprehensive Cancer Center  
Elm and Carlton Streets  
Buffalo, NY 14263