Ectopic expression of human airway trypsin‐like protease 4 in acute myeloid leukemia promotes cancer cell invasion and tumor growth

Abstract

Transmembrane serine proteases have been implicated in the development and progression of solid and hematological cancers. Human airway trypsin‐like protease 4 (HAT‐L4) is a transmembrane serine protease expressed in epithelial cells and exocrine glands. In the skin, HAT‐L4 is important for normal epidermal barrier function. Here, we report an unexpected finding of ectopic HAT‐L4 expression in neutrophils and monocytes from acute myeloid leukemia (AML) patients. Such expression was not detected in bone marrow cells from normal individuals or patients with chronic myeloid leukemia, acute lymphocytic leukemia and chronic lymphocytic leukemia. In AML patients who underwent chemotherapy, persistent HAT‐L4 expression in bone marrow cells was associated with minimal residual disease and poor prognostic outcomes. In culture, silencing HAT‐L4 expression in AML–derived THP‐1 cells by short hairpin RNAs inhibited matrix metalloproteinase‐2 activation and Matrigel invasion. In mouse xenograft models, inhibition of HAT‐L4 expression reduced the proliferation and growth of THP‐1 cell–derived tumors. Our results indicate that ectopic HAT‐L4 expression is a pathological mechanism in AML and that HAT‐L4 may be used as a cell surface marker for AML blast detection and targeting.

Characterization of the Interactions between Minocycline Hydrochloride and Trypsin with Spectroscopic and Molecular Docking Technology

“…As MC concentration increased, the position of the highest absorption peak of TRP had a red shift from 280 nm to 285 nm. The results showed that the binding of MC to the base pair of TRP resulted in a π-π * transition of amino acid residues in TRP, which reduced the energy and changed the conformation of the protein [ 27 ]. The absorbance of the maximum absorption peak of TRP increased noticeably, and only a static quenching absorption spectrum changes with a change of ground state molecule.…”

Adaptive and non-adaptive gene expression responses in prostate cancer during androgen deprivation

“…Also TMPRSS11F was identified to gain AR-association in VCaP-CT cells. This particular member of the gene family has not been widely studied but it has been reported to contribute to tumor growth and poor outcome in acute myeloid leukemia patients [ 93 ]. Nevertheless, our results suggest different role for TMPRSS11F in prostate cancer as its low expression was associated with poor progression-free survival and high Gleason score and T-stage.…”

Plant protease inhibitors as specific strategies against cancer cells

“…She is involved in processes of proliferation, invasion and metastasis in colorectal cancer. 15,16 Digestion of type II collagen by trypsin promotes invasion of the basement membrane. In addition, the activation of trypsin in tumor cells and the co-expression of MMPs facilitate invasion and metastasis.…”