KAI1(CD82) is a key molecule to control angiogenesis and switch angiogenic milieu to quiescent state

Abstract

Background Little is known about endogenous inhibitors of angiogenic growth factors. In this study, we identified a novel endogenous anti-angiogenic factor expressed in pericytes and clarified its underlying mechanism and clinical significance. Methods Herein, we found Kai1 knockout mice showed significantly enhanced angiogenesis. Then, we investigated the anti-angiogenic roll of Kai1 in vitro and in vivo. Results KAI1 was mainly expressed in pericytes rather than in endothelial cells. It localized at the membrane surface after palmitoylation by zDHHC4 enzyme and induced LIF through the Src/p53 pathway. LIF released from pericytes in turn suppressed angiogenic factors in endothelial cells as well as in pericytes themselves, leading to inhibition of angiogenesis. Interestingly, KAI1 had another mechanism to inhibit angiogenesis: It directly bound to VEGF and PDGF and inhibited activation of their receptors. In the two different in vivo cancer models, KAI1 supplementation significantly inhibited tumor angiogenesis and growth. A peptide derived from the large extracellular loop of KAI1 has been shown to have anti-angiogenic effects to block the progression of breast cancer and retinal neovascularization in vivo. Conclusions KAI1 from PC is a novel molecular regulator that counterbalances the effect of angiogenic factors.

GSK3β palmitoylation mediated by ZDHHC4 promotes tumorigenicity of glioblastoma stem cells in temozolomide-resistant glioblastoma through the EZH2–STAT3 axis

“…have been found to be regulated by palmitoylation modification [ 16 – 18 ]. ZDHHC4, a member of the ZDHHC family, has recently been shown to regulate the palmitoylation of KAI1 to localize it to the cell membrane, thereby inhibiting angiogenesis [ 19 ]. However, the role and mechanism of ZDHHC4 in the development of tumors, especially GBM, have not yet been elucidated.…”

CD82 attenuates TGF-β1-mediated epithelial-mesenchymal transition by blocking smad-dependent signaling in ARPE-19 cells

“…Cluster of differentiation 82 (CD82), also known as KAI1, is a membrane tetraspanin protein family that is expressed in various tissue types ( Lee et al, 2021 ). In many other cancer cell types, CD82 is a well-established tumor metastasis suppressor that represses the functions of motility-related proteins to restrain cell migration and invasion ( Liu and Zhang, 2006 ).…”

“…In many other cancer cell types, CD82 is a well-established tumor metastasis suppressor that represses the functions of motility-related proteins to restrain cell migration and invasion ( Liu and Zhang, 2006 ). Several studies have investigated whether CD82 has a metastasis suppressor effect via crosstalk between TGF-β and Wnt/Smad signaling, which is involved in EMT ( Zhang et al, 2019 ; Lee et al, 2021 ). Nevertheless, to date, most studies of CD82 have focused on invasive and metastatic cancer, and very few studies have focused on ocular disease ( Lee et al, 2021 ; Ye et al, 2021 ).…”

Lower expression of KAI1 as a biomarker of poor survival prognosis of melanoma combined with colorectal cancer metastasis

“…KAI1 (CD82) is a member of the quadocytosine glycoprotein superfamily and has been reported as a tumor metastasis suppressor gene in many tumor types without affecting tumor formation. 7…”

“…KAI1 (CD82) is a member of the quadocytosine glycoprotein superfamily and has been reported as a tumor metastasis suppressor gene in many tumor types without affecting tumor formation. 7 It should be noted the relationship between KAI1 and miR-633 and melanoma combined with CRC remains unclear. Therefore, the goals of this study were to explore the core genes between melanoma combined with CRC and normal tissues by using bioinformatics techniques, then verify the role of KAI1 and miR-633 in melanoma combined with CRC by examining clinical specimens.…”