Shmt2: A Stat3 signaling new player in prostate cancer energy metabolism

Ilaria Marrocco, Fabio Altieri, Elisabetta Rubini, Giuliano Paglia, Silvia Chichiarelli, Flavia Giamogante, Alberto Macone, Giacomo Perugia, Fabio Massimo Magliocca, Aymone Gurtner, Bruno Maras, Rino Ragno, Alexandros Patsilinakos, Roberto Manganaro, Margherita Eufemi

Research output: Contribution to journalArticle


Prostate cancer (PCa) is a multifactorial disease characterized by the aberrant activity of different regulatory pathways. STAT3 protein mediates some of these pathways and its activation is implicated in the modulation of several metabolic enzymes. A bioinformatic analysis indicated a STAT3 binding site in the upstream region of SHMT2 gene. We demonstrated that in LNCaP, PCa cells’ SHMT2 expression is upregulated by the JAK2/STAT3 canonical pathway upon IL-6 stimulation. Activation of SHTM2 leads to a decrease in serine levels, pushing PKM2 towards the nuclear compartment where it can activate STAT3 in a non-canonical fashion that in turn promotes a transient shift toward anaerobic metabolism. These results were also confirmed on FFPE prostate tissue sections at different Gleason scores. STAT3/SHMT2/PKM2 loop in LNCaP cells can modulate a metabolic shift in response to inflammation at early stages of cancer progression, whereas a noncanonical STAT3 activation involving the STAT3/HIF-1α/PKM2 loop is responsible for the maintenance of Warburg effect distinctive of more aggressive PCa cells. Chronic inflammation might thus prime the transition of PCa cells towards more advanced stages, and SHMT2 could represent a missing factor to further understand the molecular mechanisms responsible for the transition of prostate cancer towards a more aggressive phenotype.
Original languageEnglish
Pages (from-to)1048-1048
Number of pages1
Publication statusPublished - 2019


  • Cell metabolism
  • Prostate cancer
  • Warburg effect
  • Signaling transduction
  • STAT3
  • SHMT2


Dive into the research topics of 'Shmt2: A Stat3 signaling new player in prostate cancer energy metabolism'. Together they form a unique fingerprint.

Cite this