Crosstalk between KDEL receptor and EGF receptor mediates cell proliferation and migration via STAT3 signaling

Jia，Jie1; Zhu，Lianhui1; Yue，Xihua1; Tang，Shuocheng1; Jing，Shuaiyang1,2; Tan，Chuanting1; Du，Yulei1; Gao，Jingkai1; Lee，Intaek1; Qian，Yi1

2024-12-01

10.1186/s12964-024-01517-w

Cell Communication and Signaling   影响因子和分区

1478-811X

Hostile microenvironment of cancer cells provoke a stressful condition for endoplasmic reticulum (ER) and stimulate the expression and secretion of ER chaperones, leading to tumorigenic effects. However, the molecular mechanism underlying these effects is largely unknown. In this study, we reveal that the last four residues of ER chaperones, which are recognized by KDEL receptor (KDELR), is required for cell proliferation and migration induced by secreted chaperones. By combining proximity-based mass spectrometry analysis, split venus imaging and membrane yeast two hybrid assay, we present that EGF receptor (EGFR) may be a co-receptor for KDELR on the surface. Prior to ligand addition, KDELR spontaneously oligomerizes and constantly undergoes recycling near the plasma membrane. Upon KDEL ligand binding, the interactions of KDELR with itself and with EGFR increase rapidly, leading to augmented internalization of KDELR and tyrosine phosphorylation in the C-terminus of EGFR. STAT3, which binds the phosphorylated tyrosine motif on EGFR, is subsequently activated by EGFR and mediates cell growth and migration. Taken together, our results suggest that KDELR serves as a bona fide cell surface receptor for secreted ER chaperones and transactivates EGFR-STAT3 signaling pathway.

Clathrin EGF receptor Endosomes ERp57 Golgi GRP78 KDEL receptor STAT3

SCI

英语

其他

2-s2.0-85185487627

Scopus

1.School of Life Science and Technology,ShanghaiTech University,Pudong, Shanghai,China
2.Present address: Department of Pharmacology,School of Medicine,Southern University of Science and Technology,Shenzhen,China

Jia，Jie,Zhu，Lianhui,Yue，Xihua,et al. Crosstalk between KDEL receptor and EGF receptor mediates cell proliferation and migration via STAT3 signaling[J]. Cell Communication and Signaling,2024,22(1).

Jia，Jie.,Zhu，Lianhui.,Yue，Xihua.,Tang，Shuocheng.,Jing，Shuaiyang.,...&Qian，Yi.(2024).Crosstalk between KDEL receptor and EGF receptor mediates cell proliferation and migration via STAT3 signaling.Cell Communication and Signaling,22(1).

Jia，Jie,et al."Crosstalk between KDEL receptor and EGF receptor mediates cell proliferation and migration via STAT3 signaling".Cell Communication and Signaling 22.1(2024).