Dataset Information

Interaction between GRP78 and IGFBP-3 Affects Tumourigenesis and Prognosis in Breast Cancer Patients.

ABSTRACT: Insulin-like growth factor binding protein 3 (IGFBP-3) plays a key role in breast cancer progression and was recently shown to bind to the chaperone protein glucose-regulated protein 78 (GRP78); however, the clinical significance of this association remains poorly investigated. Here we report a direct correlation between the expression of GRP78 and IGFBP-3 in breast cancer cell lines and tumour sections. Kaplan-Meier survival plots revealed that patients with low GRP78 expression that are positive for IGFBP-3 had poorer survival rates than those with low IGFBP-3 levels, and we observed a similar trend in the publicly available METABRIC gene expression database. With breast cancer cells, in vitro IGFBP-3 enhanced induced apoptosis, however when GRP78 expression was silenced the actions of IGFBP-3 were switched from increasing to inhibiting ceramide (C2)-induced cell death and promoted cell invasion. Using immunofluorescence and cell surface biotinylation, we showed that knock-down of GRP78 negated the entry of IGFBP-3 into the cells. Together, our clinical and experimental results suggest that loss of GRP78 reduces IGFBP-3 entry into cells switching its actions to promote tumorigenesis and predicts a poor prognosis in breast cancer patients.

SUBMITTER: Zielinska HA

PROVIDER: S-EPMC7767108 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Interaction between GRP78 and IGFBP-3 Affects Tumourigenesis and Prognosis in Breast Cancer Patients.

Zielinska Hanna A HA Daly Carl S CS Alghamdi Ahmad A Bahl Amit A Sohail Muhammed M White Paul P Dean Sarah R SR Holly Jeff M P JMP Perks Claire M CM

Cancers 20201218 12

Insulin-like growth factor binding protein 3 (IGFBP-3) plays a key role in breast cancer progression and was recently shown to bind to the chaperone protein glucose-regulated protein 78 (GRP78); however, the clinical significance of this association remains poorly investigated. Here we report a direct correlation between the expression of GRP78 and IGFBP-3 in breast cancer cell lines and tumour sections. Kaplan-Meier survival plots revealed that patients with low GRP78 expression that are positi ...[more]

PMID: 33352865

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Dataset Information

Interaction between GRP78 and IGFBP-3 Affects Tumourigenesis and Prognosis in Breast Cancer Patients.

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Interaction between GRP78 and IGFBP-3 Affects Tumourigenesis and Prognosis in Breast Cancer Patients.

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