Kindlin-2 interacts with β-catenin and YB-1 to enhanceEGFRtranscription during glioma progression

Abstract

Kindlin-2 promotes carcinogenesis through regulation of cell-cell and cell-extracellular matrix adhesion. However, the role of Kindlin-2 in glioma has not been elucidated. We investigated Kindlin-2 expression in 188 human glioma tissue samples. High Kindlin-2 expression was correlated with high pathological grade and a worse prognosis. Kindlin-2 promoted glioma cell motility and proliferation both in vitro and in vivo. Importantly, Kindlin-2 activated the EGFR pathway and increased EGFR mRNA levels. In addition to up-regulating Y-box binding protein-1 (YB-1) and β-catenin expression, Kindlin-2 formed a transcriptional complex with YB-1 and β-catenin that bound to the EGFR promoter and enhanced transcription. The β-catenin/YB-1/EGFR pathway was required for Kindlin-2-mediated functions. Our data provide a better understanding of the mechanisms underlying glioma progression, and suggest that Kindlin-2 may be a biomarker and therapeutic target in glioma.

Y‐box binding protein‐1 promotes tumorigenesis and progression via the epidermal growth factor receptor/AKT pathway in spinal chordoma

“…Previous studies indicated that EGFR inhibitor markedly diminished EGFR phosphorylation in a dose‐dependent manner and suppressed proliferation of the chordoma in vitro and vivo . EGFR was transcriptionally induced by YBX1 in breast cancer and glioma . In our study, immunohistochemical staining showed that YBX1 expression was correlated to p‐EGFR and p‐Akt expression in chordoma.…”

“…As in breast cancer and glioma. 18,19 In our study, immunohistochemical staining showed that YBX1 expression was correlated to p-EGFR and p-Akt expression in chordoma. These data supported the hypothesis that YBX1 was involved in chordoma development through the EGFR pathway.…”

“…Studies have indicated that EGFR inhibitors significantly reduce the tumor growth and invasion ability of chordoma in vitro and vivo . Numerous studies have shown that YBX1 enhances EGFR expression and activates EGFR‐mediated pathways, promoting the aggressive malignant phenotypes in multiple tumors . However, to our knowledge, the functional role and regulatory mechanism of YBX1 in chordoma have not been investigated.…”

“…16,17 Numerous studies have shown that YBX1 enhances EGFR expression and activates EGFR-mediated pathways, promoting the aggressive malignant phenotypes in multiple tumors. 18,19 However, to our knowledge, the functional role and regulatory mechanism of YBX1 in chordoma have not been investigated. Based on the theoretical evidence mentioned above, we hypothesized that YBX1 is involved in the tumorigenesis and progression of chordoma through EGFR-mediated pathways.…”

Focal adhesion protein Kindlin-2 regulates bone homeostasis in mice

“…Interestingly, Yu and coworkers showed that Kindlin-2 binds to β-catenin to promote tumor cell invasion and progression. 36,37 Likewise, Lin et al showed that Kindlin-2 accelerates hepatocellular carcinoma invasion and metastasis by upregulating Wnt/β-catenin signaling. 38 Thus, Kindlin-2 can upregulate β-catenin through interactions with the latter and through an indirect mechanism involving sclerostin downregulation.…”