Secreted Heat Shock Protein 90α (HSP90α) Induces Nuclear Factor-κB-mediated TCF12 Protein Expression to Down-regulate E-cadherin and to Enhance Colorectal Cancer Cell Migration and Invasion

Abstract

Background: Both secreted HSP90␣ and overexpressed TCF12 enhance colorectal cancer (CRC) cell migration/invasion. Results: Secreted HSP90␣ induces the CD91/IB kinase/NF-B/TCF12 cascade to down-regulate E-cadherin and to enhance CRC cell migration/invasion. Conclusion: Secreted HSP90␣ acts through TCF12 expression to enhance CRC cell spreading. Significance: Secreted HSP90␣ contributes to tumor TCF12 overexpression and can be a therapeutic target of CRC.

Galacto-oligosaccharides exert a protective effect against heat stress in a Caco-2 cell model

“…These results confirmed previous findings indicating that heat shock could alter cell-cell adhesion by down-regulating E-cadherin protein levels (Lang et al, 2012). Recently, Chen, Chen, Chen, Lee, and Huang (2013) demonstrated that the underlying mechanism of E-cadherin expression during thermal stress corresponds with the HSP90-induced TCF-12 gene expression as negative regulator of E-cadherin protein. Moreover, our results clearly indicated that the heat stress-induced mRNA expression, protein derangement and delocalization of E-cadherin could be prevented by GOS pre-treatment.…”

Tumor-secreted Hsp90 Subverts Polycomb Function to Drive Prostate Tumor Growth and Invasion

“…We demonstrated a unique role for eHsp90 as an initiator of EMT events in cell-based models of prostate cancer (18), thereby providing mechanistic relevancy for its tumorigenic function. Subsequent corroboration of eHsp90 as an EMT inducer in colon cancer (19) lends support for a conserved role for eHsp90 in malignancy. Moreover, several reports have documented elevated Hsp90 in patient serum relative to cancer-free controls (20 -23), implicating a conserved clinical role for eHsp90.…”

The Endothelin-Integrin Axis Is Involved in Macrophage-induced Breast Cancer Cell Chemotactic Interactions with Endothelial Cells

“…Briefly, total cell lysates were prepared by lysing cells in buffer consisting of 10 mM Na 2 HPO 4 , 1.8 mM KH 2 PO 4 , pH 7.4, 137 mM NaCl, 2.7 mM KCl, 0.5% deoxycholate, 1% Nonidet P-40, 0.3% SDS, and 1 mM phenylmethylsulfonyl fluoride (31). Nuclear extracts were prepared according to the protocol provided in the NE-PER TM nuclear and cytoplasmic extraction reagents kit (Pierce) (29). Immunoblot analyses were performed according to the canonical procedure (31).…”

“…Preparation of Cell Protein Samples for Immunoblot Analysis-Total cell lysates and nuclear extracts were prepared as described previously (29,31). Briefly, total cell lysates were prepared by lysing cells in buffer consisting of 10 mM Na 2 HPO 4 , 1.8 mM KH 2 PO 4 , pH 7.4, 137 mM NaCl, 2.7 mM KCl, 0.5% deoxycholate, 1% Nonidet P-40, 0.3% SDS, and 1 mM phenylmethylsulfonyl fluoride (31).…”

“…These cell lines were authenticated by examining 15 tandem repeat markers (CSF1PO, D2S1338, D3S1358, D5S818, D7S820, D8S1179, D13S317, D16S539, D18S51, D19S433, D21S11, FGA, TH01, TPOX, and vWA) and the gender marker amelogenin using the AmpF/STR Identifiler PCR amplification kit (Applied Biosystems, Foster City, CA) and the American Type Culture Collection (Manassas, VA) fingerprint database. For suppressing NF-B function, MCF-7 and MDA-MB-231 cells were transfected with pRc/CMV-IB72 plasmid DNA to overexpress dominant negative IB␣ (29).…”