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

Fu, Rong; Yang, Peng; Wu, Hai; Li, Zong Wei; Li, Zhuo Yu

doi:10.7314/apjcp.2014.15.17.7245

Cited by 45 publications

(42 citation statements)

References 24 publications

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“…In addition, Derlin-1 silencing significantly inhibited the phosphorylation of PI3K, suggesting that the activation of PI3K/AKT is regulated by Derlin-1 in colon cancer cells. It is known that the activated PI3K/AKT pathway directly modulates cell growth of many types of cancer cells, including colon cancer cell [14][15][16]. Therefore, it is reasonable to speculate that the decreased cell proliferation observed in Derlin-1 shRNA-transfected SW480 cells is due to the decreased PI3K/AKT activity.…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies have shown that the PI3K/AKT pathway is critical for the proliferation of colon cancer cell [14][15][16], thus we determined whether Derlin-1 plays a role in regulating the PI3K/AKT pathway. We first examined the level of phosphorylated (active) forms of AKT in SW480 cells transfected with Derlin-1 shRNA.…”

Section: Downregulation Of Derlin-1 Inhibits Activation Of the Pi3k/amentioning

confidence: 99%

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Derlin-1 is overexpressed in human colon cancer and promotes cancer cell proliferation

Tan¹,

Jiang

et al. 2015

Mol Cell Biochem

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Derlin-1 is overexpressed in many types of solid tumors and plays an important role in cancer progression. However, the expression pattern and functions of Derlin-1 in human colon cancer are not fully understood. In the present study, we examined Derlin-1 expression in colon cancer cell lines and human tissues and investigated its role in colon cancer. We found that Derlin-1 expression was increased significantly in colon cancer tissues and its overexpression correlated with the tumor differentiation, Dukes stage, invasion, lymph node metastasis, distant metastasis, and poor overall survival. The silencing of Derlin-1 by shRNA led to the growth inhibition of colon cancer cells, which were associated with the promotion of apoptosis. Furthermore, Derlin-1 silencing significantly inhibited the activation of the PI3K/AKT signaling pathway. Taken together, our results showed that Derlin-1 is overexpressed in colon cancer and promotes proliferation of colon cancer cells. Derlin-1 may be a potential therapeutic target for the treatment of colon cancer.

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Section: Discussionmentioning

confidence: 99%

Section: Downregulation Of Derlin-1 Inhibits Activation Of the Pi3k/amentioning

confidence: 99%

Derlin-1 is overexpressed in human colon cancer and promotes cancer cell proliferation

Tan¹,

Jiang

et al. 2015

Mol Cell Biochem

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“…Corrigall et al reported that in the human immune system GRP78 has a specific, as yet unidentified receptor(s), that is expressed in myeloid lineage cells (33). Li et al showed that secreted GRP78 could utilize cell surface GRP78 on colon cancer cells as its receptor to activate intracellular signaling for proliferation (34). …”

Section: Discussionmentioning

confidence: 99%

GRP78 Impairs Production of Lipopolysaccharide-Induced Cytokines by Interaction with CD14

et al. 2017

Front. Immunol.

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The 78-kDa glucose-regulated protein (GRP78) is a stress-inducible chaperone that resides primarily in the endoplasmic reticulum. GRP78 has been described to be released at times of cellular stress and as having extracellular properties that are anti-inflammatory or favor the resolution of inflammation. In the current study, we confirmed that GRP78 impaired the production of lipopolysaccharide-induced pro-inflammatory cytokines in GRP78-treated bone-marrow-derived dendritic cells (DCs). To explore the underlying mechanism, first of all, GRP78 was checked to be bound to the plasma membrane. Interestingly, such binding promoted endocytosis of toll-like receptor (TLR) 4 and reduction in TLR4 on the plasma surface had a key role in desensitization of GRP78-treated DCs to lipopolysaccharide. Given that cluster of differentiation (CD)14 is a crucial regulator of TLR4 endocytosis, interaction of GRP78 with CD14 was investigated next. Data showed that GRP78 co-localized with CD14 on the plasma membrane and glutathione-S-transferase-GRP78 precipitated CD14. In CD14 knockout mice, down-regulation of tumor necrosis factor-α and reduction in TLR4 on the plasma surface were abrogated in GRP78-treated DCs. Overall, these data suggested that GRP78 mediates endocytosis of TLR4 by targeting CD14 to favor the resolution of inflammation.

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“…GRP78 has been observed to be elevated in hepatocellular carcinoma, prostate, glioma, oral cancer, breast and gastric cancers. In many cancers, high GRP78 levels have been found to correlate with higher pathological grade and aggressive phenotype (52, 53, 54). Furthermore, autoantibodies against GRP78 have been observed in sera of prostate cancer patients and showed positive correlation with the aggressiveness of the disease (55).…”

Section: Atf6: the Least Well Understood Arm Of The Uprmentioning

confidence: 99%

Targeting the unfolded protein response in cancer

Ojha

Amaravadi

2017

Pharmacological Research

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Cancer cells are exposed to various intrinsic and extrinsic factors that disrupt protein homeostasis, producing endoplasmic reticulum (ER) stress. To cope with these situations, cancer cells evoke a highly conserved adaptive mechanism called the unfolded protein response (UPR) to restore the ER homeostasis. Recently, several pharmacological agents have been found to exhibit anti-tumor activity by targeting the UPR components. The development of potent and specific compounds that target the UPR components has not only shed light on the regulation of the UPR in cancer cells, but also brought the field closer to clinical drug candidates. Here we present an overview of the milestones in the field of UPR biology in cancer with a focus on new strategies for pharmacological inhibition.

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

Cited by 45 publications

References 24 publications

Derlin-1 is overexpressed in human colon cancer and promotes cancer cell proliferation

Derlin-1 is overexpressed in human colon cancer and promotes cancer cell proliferation

GRP78 Impairs Production of Lipopolysaccharide-Induced Cytokines by Interaction with CD14

Targeting the unfolded protein response in cancer

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