Transmembrane chemokines act as receptors in a novel mechanism termed inverse signaling

ELife
Kirsten HattermannRolf Mentlein

Abstract

The transmembrane chemokines CX3CL1/fractalkine and CXCL16 are widely expressed in different types of tumors, often without an appropriate expression of their classical receptors. We observed that receptor-negative cancer cells could be stimulated by the soluble chemokines. Searching for alternative receptors we detected that all cells expressing or transfected with transmembrane chemokine ligands bound the soluble chemokines with high affinity and responded by phosphorylation of intracellular kinases, enhanced proliferation and anti-apoptosis. This activity requires the intracellular domain and apparently the dimerization of the transmembrane chemokine ligand. Thus, shed soluble chemokines can generate auto- or paracrine signals by binding and activating their transmembrane forms. We term this novel mechanism "inverse signaling". We suppose that inverse signaling is an autocrine feedback and fine-tuning system in the communication between cells that in tumors supports stabilization and proliferation.

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Citations

Mar 8, 2017·PloS One·Andrea KoenenDaniela Dreymueller
Feb 22, 2018·Glia·Valéria Pereira FerrerRolf Mentlein
Mar 3, 2017·Journal of Immunology Research·Katja SpiessMette M Rosenkilde
Jul 13, 2017·International Journal of Molecular Sciences·Vivian AdamskiKirsten Hattermann
May 21, 2020·Proceedings of the National Academy of Sciences of the United States of America·Romi GuptaNarendra Wajapeyee
Jun 5, 2020·Scientific Reports·Mariano A OstuniPhilippe Deterre
Feb 16, 2019·Frontiers in Immunology·Adam M SandorRachel S Friedman
Apr 29, 2020·Cancers·Balsam Rizeq, Mohammed Imad Malki
May 4, 2020·Developmental and Comparative Immunology·Dan HeYan Li
Apr 4, 2021·International Journal of Molecular Sciences·Jan KorbeckiIrena Baranowska-Bosiacka
Apr 4, 2021·International Journal of Molecular Sciences·Deniz CayliogluJanka Held-Feindt

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Methods Mentioned

BETA
FCS
fluorescence microscopy
light microscopy
transfection
ELISA
FACS
X-ray
PCR
electrophoresis
flow

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