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The TGF-b Signaling Regulator PMEPA1 Suppresses Prostate Cancer Metastases to Bone

Fournier, P. et al. Cancer Cell 2015.

Transforming growth factor-beta (TGF-beta) is the main factor released from the bone mineral matrix that drives the growth of cancer cells in bone. Therefore TGF-beta represents an attractive therapeutic target and we have shown that small molecule inhibitors of TGF-beta signaling are efficient for the treatment of bone metastases. We applied whole transcriptome analysis to identify multiple target genes that could be used as new targets for the treatment of bone metastases or that could be used as predictive markers. Among those, we identified a new gene called PMEPA1 that inhibits TGF-beta signaling in cancer cells. We determined that loss of expression of PMEPA1 in cancer cells increases bone metastases in mice. We also determined that low expression of PMEPA1 in the primary tumor of breast cancer patients is associated with a decreased survival as well as a decreased time to the occurrence of metastases. We are now investigating how PMEPA1 is affecting tumor initiation whether PMEPA1 expression could be used for diagnostic purposes in cancer patients.

Source: Fournier, P. et al. Cancer Cell, 2015.