Glucose regulated protein 78: A critical link between tumor microenvironment and cancer hallmarks

Li, Zongwei; Li, Zhuoyu

doi:10.1016/j.bbcan.2012.02.001

Cited by 98 publications

(123 citation statements)

References 145 publications

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“…GRP78 is overexpressed in different human cancer types, including gastric cancer, and is associated with the growth, invasion and metastasis of tumors (16)(17)(18)(19)(20). Inhibition of GRP78 activities reduces tumor formation of gastric cancer cells in xenograft models and suppresses proliferation, invasion and drug resistance in gastric cancer cells (33).…”

Section: Discussionmentioning

confidence: 99%

“…GRP78 is a stress-inducible molecular chaperone that is upregulated in cancer cells with increasing hypoxia, nutrient starvation and acidosis (16,17). GRP78 is overexpressed in different human cancer types, including gastric cancer, and is associated with the growth, invasion and metastasis of tumors (16)(17)(18)(19)(20).…”

Section: Discussionmentioning

confidence: 99%

“…Additionally, GRP78 is a stress-response protein that is upregulated disturbances to cellular homeostasis, including reduced levels of oxygen or glucose, and is translocated from the endoplasmic reticulum to other cellular locations, including the nucleus or the plasma membrane, where it functions as a membrane receptor to transduce proliferation, invasion, apoptosis, inflammation and immunity signals (16,17 documented in a number of cancer cell lines and tissues and is associated with aggressive growth and invasive properties (18)(19)(20). Upregulation of GRP78 expression is associated with increased lymph node metastasis and poor prognosis in patients with gastric cancer (21).…”

Section: Introductionmentioning

confidence: 99%

“…The 78 kDa glucose-regulated protein (GRP78) is an endoplasmic reticulum chaperone that functions as a regulator of intracellular calcium, protein folding and the unfolded-protein response (16,17). Additionally, GRP78 is a stress-response protein that is upregulated disturbances to cellular homeostasis, including reduced levels of oxygen or glucose, and is translocated from the endoplasmic reticulum to other cellular locations, including the nucleus or the plasma membrane, where it functions as a membrane receptor to transduce proliferation, invasion, apoptosis, inflammation and immunity signals (16,17 documented in a number of cancer cell lines and tissues and is associated with aggressive growth and invasive properties (18)(19)(20).…”

Section: Introductionmentioning

confidence: 99%

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Estrogen receptor‑α36‑mediated rapid estrogen signaling regulates 78 kDa glucose‑regulated protein expression in gastric carcinoma cells

Wang

et al. 2018

Oncol Lett

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Abstract.To determine whether estrogen receptor-α36 (ER-α36) -mediated rapid estrogen signaling is associated with 78 kDa glucose-regulated protein (GRP78) expression in gastric cancer, 86 samples of gastric tumor tissue with corresponding normal and tumor-adjacent tissues were used to examine expression patterns of GRP78 and ER-α36. Immunohistochemistry demonstrated that 55/86 (63.95%) patients with gastric carcinoma, and western blot analysis revealed that GRP78 was upregulated in 15/20 (75%) of tumor specimens. GRP78 expression was positively associated with ER-α36 expression, the male sex and lymph node metastasis (P<0.05). Estrogen treatment increased GRP78 and ER-α36 expression, as well as GSK-3β phosphorylation in established gastric cancer SGC-7901 cells. The steady-state level of GRP78 protein expression and the level of phosphorylated GSK-3β at Ser9 were decreased in SGC-7901 cells with ER-α36 knockdown. Forced expression of ER-α36 in SGC-7901 cells, however, led to an increase in GRP78 expression and GSK-3β phosphorylation. It may therefore be concluded that ER-α36-mediated rapid estrogen signaling positively regulates GRP78 expression, presumably via the GSK-3β pathway, which may be associated with gastric carcinogenesis.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Estrogen receptor‑α36‑mediated rapid estrogen signaling regulates 78 kDa glucose‑regulated protein expression in gastric carcinoma cells

Wang

et al. 2018

Oncol Lett

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“…GRP78 is usually overexpressed in tumor cells, and implicated in tumor cell survival, angiogenesis, metastasis and therapy resistance (Lee, 2007;Vlashi et al, 2011;Li and Li, 2012). GRP78 is also involved in transcriptional activation of proinflammatory cytokine genes and is a valid therapeutic target for prevention of liver cancer (Wang et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

GRP78 Secreted by Colon Cancer Cells Facilitates Cell Proliferation via PI3K/Akt Signaling

Fu¹,

Yang²,

Wu³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Glucose regulated protein 78 (GRP78) is usually recognized as a chaperone in the endoplasmic reticulum. However, increasing evidence indicates that GRP78 can be translocated to the cell surface, acting as a signaling receptor for a variety of ligands. Since little is known about the secretion of GRP78 and its role in the progression of colon cancer we here focused on GRP78 from colon cancer cells, and purified GRP78 protein mimicking the secreted GRP78 was able to utilize cell surface GRP78 as its receptor, activating downstream PI3K/Akt and Wnt/β-catenin signaling and promote colon cancer cell proliferation. Our study revealed a new mode of action of autocrine GRP78 in cancer progression: secreted GRP78 binds to cell surface GRP78 as its receptor and activates intracellular proliferation signaling.

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Extracellular glucose level regulates dependence on GRP78 for cell surface localization of multipass transmembrane proteins in HeLa cells

et al. 2018

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Many human-cultured cell lines survive glucose starvation, but the underlying mechanisms remain unclear. Here, we searched for proteins required for cellular adaptation to glucose-limited conditions and identified several endoplasmic reticulum chaperones in the glucose-regulated protein (GRP) family as proteins enriched in the cellular membrane. Surprisingly, these proteins, which are required for cell surface localization of GLUT1 under high-glucose conditions, become dispensable for targeting GLUT1 to the surface upon glucose starvation. In marked contrast, cell surface localization of single-pass transmembrane proteins, such as epidermal growth factor receptor and CD98, is not disturbed by GRP78 depletion regardless of the extracellular glucose level. These results indicate that the extracellular glucose level regulates dependence on the GRPs for cell surface localization of multipass transmembrane proteins.

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Glucose regulated protein 78: A critical link between tumor microenvironment and cancer hallmarks

Cited by 98 publications

References 145 publications

Estrogen receptor‑α36‑mediated rapid estrogen signaling regulates 78 kDa glucose‑regulated protein expression in gastric carcinoma cells

Estrogen receptor‑α36‑mediated rapid estrogen signaling regulates 78 kDa glucose‑regulated protein expression in gastric carcinoma cells

GRP78 Secreted by Colon Cancer Cells Facilitates Cell Proliferation via PI3K/Akt Signaling

Extracellular glucose level regulates dependence on GRP78 for cell surface localization of multipass transmembrane proteins in HeLa cells

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