The gene identified by researchers based on genetic data diagnosed in a cohort of 159 lung cancer patients suppresses a common cell-signaling pathway that in the majority of cases serves as a cancer suppressor.

Persistent inhibition of this pathway by EGFR and TRIM87 that drives resistance to temozolomide (TMZ) was recently described by professors Carlo Fenicelli from the Department of Pathology of the University of Trento Italy and Andreas Aube from the Department of Advanced Science and Technology of the University of Basel in Switzerland.

Research by Aubes team found that when the STAT1 gene is treated with temozolomide (TMZ) the inhibition of calcium signaling resulting from an increase in the expression of an intracellular signal is reversed.

The study published in Cell Reports describes the role of STAT3 (Caress-1) in modulating the signaling pathways in fight against cell- and molecular-based cancers.

Calcium homeostasis is regulated by the intracellular signal Caress-1. Without Caress-1 expression three responses to intracellular stresses are observed: an accumulation of calcium in the extracellular environment an increase in intracellular Co-P-ELAS1 (target dwarf-1) and expression of inhibitor of calcium ligand UGT1 (target long-superm-1). In a dose-dependent manner STAT1 increases the levels of Caress-1 and TRIM87 enhancing calcium uptake.

Two experiments were performed to assess the influence of STAT1 and TRIM87 signaling on Caress-1 and EGFR- activation in PBMC patients.

The results of the studies provided evidence that tyrosine kinase protein 3 (TK3) inhibition promotes Caress-1 expression and that this boosting of Caress-1 is initiated by an increase in TK3 binding to mitragynine 1 (MIL1) in protective macrophages against both GP-defined and non-GP-defined lung cancers.

The results also identified that the dose-dependent increase in the expression of TK3 prevents recruitment of another pro-micro-environment response to prevent the progression of non-detected lung cancers.