Jak kinase activity is required for lymphoma invasion and metastasis

Oncogene
Frank J M OpdamEd Roos

Abstract

Jak tyrosine kinases are activated by interleukins and other growth factors, and promote survival and proliferation of cells in multiple tissues. These kinases are constitutively active in many hematopoietic malignancies and certain carcinomas. We have investigated whether Jak kinases play a role in lymphoma invasion and metastasis. Proliferation and survival of a highly metastatic T-lymphoma was made independent of its constitutively active Jak by expression of active forms of both STAT3 and PI3-kinase. Jak activity was then blocked by the isolated JH2 'pseudokinase' domain of Jak2. In vitro invasion was blocked by the JH2 domain, and the metastatic capacity of the JH2-expressing cells was much reduced. The Jak inhibitor AG490 inhibited invasion as well. Invasion and metastasis of these cells requires activation of the integrin LFA-1 by the CXCR4 chemokine receptor. We show that Jak kinases act downstream of LFA-1. We conclude that Jak kinase activity is essential for lymphoma invasion and metastasis, independent of its role in survival and proliferation, and independent of STAT and PI3K signaling. This indicates that Jak kinases contribute in multiple ways to the induction of malignant behavior.

References

Apr 1, 1993·Journal of Leukocyte Biology·G La RivièreE Roos
Jun 1, 1996·Current Opinion in Immunology·A C Chan, A S Shaw
May 23, 1998·Annual Review of Immunology·W J Leonard, J J O'Shea
Sep 10, 1998·The Journal of Cell Biology·R D SoedeE Roos
Mar 31, 1999·Proceedings of the National Academy of Sciences of the United States of America·J M Rodríguez-FradeM Mellado
Aug 24, 1999·Cell·J F BrombergJ E Darnell
Apr 25, 2000·Molecular and Cellular Biology·P SaharinenO Silvennoinen
Mar 20, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·R D SoedeE Roos
Mar 30, 2001·The Journal of Biological Chemistry·H E TibblesF M Uckun
Jul 18, 2001·The Journal of Clinical Investigation·I S ZeelenbergE Roos
May 8, 2002·The Journal of Clinical Investigation·Jacqueline Bromberg
Oct 24, 2002·Blood·Joachim RolandMartine Biard-Piechaczyk
Dec 14, 2002·Developmental Cell·Steven X HouNorbert Perrimon
May 6, 2003·European Journal of Immunology·Silvia F SorianoMario Mellado

❮ Previous
Next ❯

Citations

Aug 6, 2005·Proceedings of the National Academy of Sciences of the United States of America·Pilar BlancafortCarlos F Barbas
Jan 26, 2016·Cellular Signalling·Shirley C MillsAnja Mueller
Nov 4, 2009·The Korean Journal of Physiology & Pharmacology : Official Journal of the Korean Physiological Society and the Korean Society of Pharmacology·In Ae SeoHwan Tae Park
May 21, 2009·British Journal of Cancer·M PfeifferM Burger
Apr 16, 2015·American Journal of Clinical Pathology·Ya-Ping ChenKung-Chao Chang
Apr 3, 2010·Journal of Neuro-oncology·Qinglin LiuJian Zhang

❮ Previous
Next ❯

Related Concepts

Related Feeds

AKT Pathway

This feed focuses on the AKT serine/threonine kinase, which is an important signaling pathway involved in processes such as glucose metabolism and cell survival.

Adhesion Molecules in Health and Disease

Cell adhesion molecules are a subset of cell adhesion proteins located on the cell surface involved in binding with other cells or with the extracellular matrix in the process called cell adhesion. In essence, cell adhesion molecules help cells stick to each other and to their surroundings. Cell adhesion is a crucial component in maintaining tissue structure and function. Discover the latest research on adhesion molecule and their role in health and disease here.