CD151 knockdown inhibits osteosarcoma metastasis through the GSK-3β/β-catenin/MMP9 pathway

Abstract

Osteosarcoma (OS) is a primary bone malignancy with a high early metastatic propensity. It is crucial to find specific protein targets to develop therapeutic strategies against this lethal disease. Tetraspanin CD151 is involved in facilitating tumor metastasis. However, the role and molecular mechanism of CD151 in promoting OS metastasis remain enigmatic. In the present study, we used small interfering RNA (siRNA) to inhibit CD151 expression in highly metastatic OS cells and the results demonstrated that CD151 knockdown inhibited their migration, invasion and metastasis. We further investigated the molecular mechanism of CD151 by inhibiting genes known to be involved in metastasis in OS cells and found that CD151 modulated matrix metalloproteinase 9 (MMP9) expression through the glycogen synthase kinase 3 (GSK-3β)/β-catenin signaling pathway. We conclude that CD151 knockdown inhibits the expression of MMP9 through the GSK-3β/β‑catenin pathway and also inhibits OS migration and invasion in vitro and metastasis in vivo in highly metastatic OS. This suggests that CD151 may be a useful antimetastatic target for OS.

TSPAN31 is a critical regulator on transduction of survival and apoptotic signals in hepatocellular carcinoma cells

“…β‐catenin is a key molecule of the Akt signaling pathway, and migrates from cytoplasm to cell nucleus to activate the Akt pathway . Some members of the tetraspanin family have been reported to inhibit β‐catenin degradation . We have observed that TSPAN31 knockdown reduced the expression of Akt signaling pathway component β‐catenin.…”

Tetraspanin CD151 mediates communication between prostate cancer cells and osteoblasts

“…3B). The obtained zymogram showed that although there was no bands associated with function of MMP-2 (72 kDa) or MMP-9 (92 kDa) (both shown to be regulated by CD151 (Yanez-Mo et al, 2008;Zhang et al, 2016)), a clear CD151-dependent digestive activity, located at molecular weight of approx. 48 kDa, typical for MMP-13 was observed (Fig.…”

Exosomal tetraspanins mediate cancer metastasis by altering host microenvironment

“…The proteomic analysis demonstrates that package proteins of exosomes are specific and are completely different from cell apoptosis by the release of apoptotic bodies [ 68 , 69 ]. The High Throughput Sequencing technology verifies that the miRNA is also subject to certain mechanisms rather than a random package of exosomes [ 70 ].…”

“…Furthermore, Tspan8 mediates tumor cell motility and invasion [ 72 , 90 ]. Tetraspanin CD151 has been shown to be involved in tumor cell motility, invasion, metastasis and angiogenesis [ 69 , 70 ]. CD9 is considered to be a tumor suppressor and facilitates tumor angiogenesis [ 76 , 91 ].…”