Spi-B–Mediated Silencing of Claudin-2 Promotes Early Dissemination of Lung Cancer Cells from Primary Tumors

Abstract

Dissociation from epithelial sheets and invasion through the surrounding stroma are critical early events during epithelial cancer metastasis. Here we find that a lymphocyte lineage-restricted transcription factor, Spi-B, is frequently expressed in human lung cancer tissues. The Spi-B-expressing cancer cells coexpressed vimentin but repressed E-cadherin and exhibited invasive behavior. Increased Spi-B expression was associated with tumor grade, lymphatic metastasis, and short overall survival. Mechanistically, Spi-B disrupted intercellular junctions and enhanced invasiveness by reconfiguring the chromatin structure of the tight junction gene claudin-2 (CLDN2) and repressing its transcription. These data suggest that Spi-B participates in mesenchymal invasion, linking epithelial cancer metastasis with a lymphatic transcriptional program.

SPIB promotes anoikis resistance via elevated autolysosomal process in lung cancer cells

“…8B,C). Consistent with our previous observation, autophagy deficiency increases CLDN2 protein levels and inhibits anchorage-independent cell growth [15]. Thus, these data indicate that SPIB-mediated transcriptional regulation is involved in anoikis resistance in lung cancer cells.…”

Polymorphisms in TWIST1 and ZEB1 Are Associated with Prognosis of Gastric Cancer Patients

“…This tool revealed that rs6953766 creates a binding site for Spi-B transcription factor. It is an Ets family TF expressed exclusively in mature B cells, T-cell progenitors and plasmacytoid dendritic cells (30). Nevertheless, Jian et al (31) reported that Spi-B is one of the twenty TFs overexpressed in GC tumors compared to normal tissues.…”

“…Nevertheless, Jian et al (31) reported that Spi-B is one of the twenty TFs overexpressed in GC tumors compared to normal tissues. Recently, Du et al (30) published the results of a study of this TF in NSCLC tumors. They found that high Spi-B expression is associated with worst prognosis.…”

A gene expression signature‐based nomogram model in prediction of breast cancer bone metastases

“…37 The third gene SPIB, encoding an ETS-domain transcription factor, was believed to be associated with cancers especially in lymphomas. 38,39 Also, Yi-Jung et al 40 found the SPIB may be involved in tumorigenesis in live cancer, and Wei et al 41 reported that SPIB is expressed in invasive cancer cells in human primary lung cancer tissues. ALDH3B2 was widely known as a member of aldehyde dehydrogenases (ALDHs).…”