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...
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doaj-3fd4a31b2861474aab98ba40920b2e082020-11-25T01:37:20ZengWileyCancer Medicine2045-76342019-05-01852348235910.1002/cam4.2074Ectopic expression of human airway trypsin‐like protease 4 in acute myeloid leukemia promotes cancer cell invasion and tumor growthRuhong Yan0Meng Liu1Yae Hu2Lina Wang3Can Wang4Yizhi Jiang5Quansheng Zhou6Xiaofei Qi7Ningzheng Dong8Qingyu Wu9Cyrus Tang Hematology Center, Collaborative Innovation Center of Hematology, State Key Laboratory of Radiation Medicine and Prevention Soochow University Suzhou ChinaCyrus Tang Hematology Center, Collaborative Innovation Center of Hematology, State Key Laboratory of Radiation Medicine and Prevention Soochow University Suzhou ChinaCyrus Tang Hematology Center, Collaborative Innovation Center of Hematology, State Key Laboratory of Radiation Medicine and Prevention Soochow University Suzhou ChinaCyrus Tang Hematology Center, Collaborative Innovation Center of Hematology, State Key Laboratory of Radiation Medicine and Prevention Soochow University Suzhou ChinaCyrus Tang Hematology Center, Collaborative Innovation Center of Hematology, State Key Laboratory of Radiation Medicine and Prevention Soochow University Suzhou ChinaCyrus Tang Hematology Center, Collaborative Innovation Center of Hematology, State Key Laboratory of Radiation Medicine and Prevention Soochow University Suzhou ChinaCyrus Tang Hematology Center, Collaborative Innovation Center of Hematology, State Key Laboratory of Radiation Medicine and Prevention Soochow University Suzhou ChinaCyrus Tang Hematology Center, Collaborative Innovation Center of Hematology, State Key Laboratory of Radiation Medicine and Prevention Soochow University Suzhou ChinaCyrus Tang Hematology Center, Collaborative Innovation Center of Hematology, State Key Laboratory of Radiation Medicine and Prevention Soochow University Suzhou ChinaCyrus Tang Hematology Center, Collaborative Innovation Center of Hematology, State Key Laboratory of Radiation Medicine and Prevention Soochow University Suzhou ChinaAbstract 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.https://doi.org/10.1002/cam4.2074Acute myeloid leukemia (AML)cancer progressionhuman airway trypsin‐like protease 4 (HAT‐L4)matrix metalloproteinase (MMP)type II transmembrane serine protease (TTSP) |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Ruhong Yan Meng Liu Yae Hu Lina Wang Can Wang Yizhi Jiang Quansheng Zhou Xiaofei Qi Ningzheng Dong Qingyu Wu |
spellingShingle |
Ruhong Yan Meng Liu Yae Hu Lina Wang Can Wang Yizhi Jiang Quansheng Zhou Xiaofei Qi Ningzheng Dong Qingyu Wu Ectopic expression of human airway trypsin‐like protease 4 in acute myeloid leukemia promotes cancer cell invasion and tumor growth Cancer Medicine Acute myeloid leukemia (AML) cancer progression human airway trypsin‐like protease 4 (HAT‐L4) matrix metalloproteinase (MMP) type II transmembrane serine protease (TTSP) |
author_facet |
Ruhong Yan Meng Liu Yae Hu Lina Wang Can Wang Yizhi Jiang Quansheng Zhou Xiaofei Qi Ningzheng Dong Qingyu Wu |
author_sort |
Ruhong Yan |
title |
Ectopic expression of human airway trypsin‐like protease 4 in acute myeloid leukemia promotes cancer cell invasion and tumor growth |
title_short |
Ectopic expression of human airway trypsin‐like protease 4 in acute myeloid leukemia promotes cancer cell invasion and tumor growth |
title_full |
Ectopic expression of human airway trypsin‐like protease 4 in acute myeloid leukemia promotes cancer cell invasion and tumor growth |
title_fullStr |
Ectopic expression of human airway trypsin‐like protease 4 in acute myeloid leukemia promotes cancer cell invasion and tumor growth |
title_full_unstemmed |
Ectopic expression of human airway trypsin‐like protease 4 in acute myeloid leukemia promotes cancer cell invasion and tumor growth |
title_sort |
ectopic expression of human airway trypsin‐like protease 4 in acute myeloid leukemia promotes cancer cell invasion and tumor growth |
publisher |
Wiley |
series |
Cancer Medicine |
issn |
2045-7634 |
publishDate |
2019-05-01 |
description |
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. |
topic |
Acute myeloid leukemia (AML) cancer progression human airway trypsin‐like protease 4 (HAT‐L4) matrix metalloproteinase (MMP) type II transmembrane serine protease (TTSP) |
url |
https://doi.org/10.1002/cam4.2074 |
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