Cytoskeleton-associated membrane protein�4 is upregulated in tumor tissues and is associated with clinicopathological characteristics and prognosis in hepatocellular carcinoma

Chen, Zhiyong; Wang, Ting; Gan, Xia; Chen, Sihai; He, Yuting; Wang, Yuqi; Zhang, Kun‐He

doi:10.3892/ol.2020.11499

Cited by 4 publications

(8 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Clinical evidence suggested that DKK1 is positively involved in tumorigenesis, but the underlying mechanism where DKK1 promotes tumor growth has remained unclear for a long time (13)(14)(15). It has been found that the binding of DKK1 to CKAP4 activates Ak strain transforming (AKT) via phosphoinositide 3-kinase (PI3K) and that overexpression of DKK1 and CKAP4 is observed in pancreatic, esophageal, and liver cancers (11,(16)(17)(18), while an anti-CKAP4 antibody, which blocks DKK1 binding to CKAP4, inhibited in vivo tumor formation by pancreatic cancer cells (19). In terms of lung cancer, immunohistochemically high DKK1 expression levels in NSCLC patients are associated with poor prognoses, and serum DKK1 levels have been shown to become a clinical marker (20,21).…”

Section: Introductionmentioning

confidence: 99%

CKAP4 is a potential exosomal biomarker and therapeutic target for lung cancer

Nagoya¹,

Sada²,

Kimura³

et al. 2023

Transl Lung Cancer Res

View full text Add to dashboard Cite

Background: Globally, lung cancer causes the most cancer death. While molecular therapy progress, including epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), has provided remarkable therapeutic effects, some patients remain resistant to these therapies and therefore new target development is required. Cytoskeleton-associated membrane protein 4 (CKAP4) is a receptor of the secretory protein Dickkopf-1 (DKK1) and the binding of DKK1 to CKAP4 promotes tumor growth via Ak strain transforming (AKT) activation. We investigated if CKAP4 functions as a diagnostic biomarker and molecular therapeutic target for lung cancer.Methods: CKAP4 secretion with exosomes from lung cancer cells and the effect of CKAP4 palmitoylation on its trafficking to the exosomes were examined. Serum CKAP4 levels were measured in mouse xenograft models, and 92 lung cancer patients and age-and sex-matched healthy controls (HCs). The lung cancer tissues were immunohistochemically stained for DKK1 and CKAP4, and their correlation with prognosis and serum CKAP4 levels were investigated. Roles of CKAP4 in the lung cancer cell proliferation were examined, and the effects of the combination of an anti-CKAP4 antibody and osimertinib, a third generation TKI, on anti-tumor activity were tested using in vitro and in vivo experiments.Results: CKAP4 was released from lung cancer cells with exosomes, and its trafficking to exosomes was regulated by palmitoylation. CKAP4 was detected in sera from mice inoculated with lung cancer cells overexpressing CKAP4. In 92 lung cancer patients, positive DKK1 and CKAP4 expression patients showed worse prognoses. Serum CKAP4 positivity was higher in lung cancer patients than in HCs. After surgical operation, serum CKAP4 levels were decreased. CKAP4 overexpression in lung cancer cells promoted in vitro cell proliferation and in vivo subcutaneous tumor growth, which were inhibited by an anti-CKAP4 antibody. Moreover, treatment with this antibody or osimertinib, a third generation TKI, inhibited AKT activity, sphere formation, and xenograft tumor growth in lung cancer cells harboring EGFR mutations and expressing both DKK1 and CKAP4, while their combination showed stronger inhibition.Conclusions: CKAP4 may represent a novel biomarker and molecular target for lung cancer, and combination therapy with an anti-CKAP4 antibody and osimertinib could provide a new lung cancer therapeutic strategy.

show abstract

Section: Introductionmentioning

confidence: 99%

CKAP4 is a potential exosomal biomarker and therapeutic target for lung cancer

Nagoya¹,

Sada²,

Kimura³

et al. 2023

Transl Lung Cancer Res

View full text Add to dashboard Cite

show abstract

“…Himburg et al (28) reported that DKK1 treatment induced EGF secretion in bone marrow cells; with our findings here, this raises the possibility that DKK1 and EGF may establish a positive feedback loop in HCC and accelerate tumor metastasis. DKK1 has been reported to perform its biological functions by binding to its receptors cytoskeleton-associated membrane protein 4 (CKAP4) or LRP5/6, which are significantly elevated in HCC tumor tissues (29)(30)(31)(32). Although aberrantly increased CKAP4 or LRP5/6 is positively correlated with tumor progression (31,33), it remains to be investigated whether EGF has an effect on the expression of CKAP4 or LRP5/6 in HCC cells in our future work.…”

Section: Discussionmentioning

confidence: 93%

“…DKK1 has been reported to perform its biological functions by binding to its receptors cytoskeleton-associated membrane protein 4 (CKAP4) or LRP5/6, which are significantly elevated in HCC tumor tissues (29)(30)(31)(32). Although aberrantly increased CKAP4 or LRP5/6 is positively correlated with tumor progression (31,33), it remains to be investigated whether EGF has an effect on the expression of CKAP4 or LRP5/6 in HCC cells in our future work. We think this will help us understand the complexity of possible positive loop interactions involving EGF and DKK1 signaling.…”

Section: Discussionmentioning

confidence: 93%

EGF promotes DKK1 transcription in hepatocellular carcinoma by enhancing the phosphorylation and acetylation of histone H3

Niu

Liang

et al. 2020

Sci. Signal.

View full text Add to dashboard Cite

The protein Dickkopf-1 (DKK1) is frequently overexpressed at the transcript level in hepatocellular carcinoma (HCC) and promotes metastatic progression through the induction of β-catenin, a Wnt signaling effector. We investigated how DKK1 expression is induced in HCC and found that activation of the epidermal growth factor receptor (EGFR) promoted parallel MEK-ERK and PI3K-Akt pathway signaling that converged to epigenetically stimulate DKK1 transcription. In HCC cell lines stimulated with EGF, EGFR-activated ERK phosphorylated the kinase PKM2 at Ser37, which promoted its nuclear translocation. Also in these cells, EGFR-activated Akt phosphorylated the acetyltransferase p300 at Ser1834. Subsequently, PKM2 and p300 mediated the phosphorylation and acetylation, respectively, of histone H3 at the DKK1 promoter, which synergistically enhanced DKK1 transcription. The mechanism was supported with mutational analyses in cells and in a chemically induced HCC model in rats. The findings suggest that dual inhibition of the MEK and PI3K pathways might suppress the expression of DKK1 and, consequently, tumor metastasis in patients with HCC.

show abstract

“…CKAP4 protein is upregulated in hepatocellular carcinoma tissues and has been identi ed as speci cally in it [31]. FBXW11, a F-box family members contributing to tumorigenesis and tumour development [32]; [33].…”

Section: Discussionmentioning

confidence: 99%

Identification of potent novel biomarkers related to Osteoporosis through bioinformatics approach

Khusboo

Bhushan

Kusum

et al. 2022

Preprint

View full text Add to dashboard Cite

Objective Calcium is fundamental component of bone tissue. It is present in extracellular fluid in ionized form, some are bounded with albumin while a few are of the complex anionic form. Calcium regulates many biochemical processes. Loss of calcium causes hypocalcemia further lead to osteopenia and osteoporosis. Proton pump inhibitor causes mal-absorption of calcium that leads to poor bone metabolism might causes hip fracture. Some studies via microRNA gene regulatory networks have been analyzed in the present study. Methods Microarray gene expression dataset has been retrieved by using NCBI gene expression Omnibus (GEO) database. Benjomini and Hochberg algorithm was used for identifying DEG’s and pre-processing of datasets. Heatmap plot and principal component analysis plot were generated by using online tool ClustVis for DEG’s. PPI network and sub network were analyzed by finding functional interactions among protein via online tool STRING v 10.5. DEG’s functional pathways analysis has been done by using DAVID (Database for Annotation, Visualization and Integration Discovery) software. Results A number of 3390 differentially expressed genes (DEG’s) were identified. …..were up-regulated and were down-regulated genes. DEGs related to Hypocalcemia and Bone signaling were 53, osteogenesis and bone signaling both were 86, whereas, 8 DEG’s related to hypocalcemia, Osteogenesis, and Bone signaling. The network of protein-protein interaction and sub network was having ITCH, CKAP4(Up) and FBXW11, RAB37(down) DEGs were concerned in hypocalcemia and were forming hub nodes while CHML, ATP11A, TMEM30A (Up) and YWHAE, AP1M1, FYN(down) DEG’s forming were all related to bone signaling. Functional enrichment analysis was performed notably enriched major molecular functions, biological processes and cellular components of novel DEG’s (FDR<0.05) related to hypocalcemia and osteoporosis were found. Conclusion Thus by concluding the genes ie; ITCH, CKAP4, FBXW11, RAB37, CHML, ATP11A, TMEM30A, YWHAE, AP1M1, FYN, CTNNB1, UBE2D1, RAP1A, EGFR, MAPK1 and AKT1, whether are unregulated or downregulatd in the diseased tissue samples, and plays a essential role in disease progression. These hub genes are occupied in different biological, molecular and cellular functions which might be related to bone signaling or osteoporosis. For the further cross validation wet lab experiments are required to validate gene roles.

show abstract

Cytoskeleton-associated membrane protein�4 is upregulated in tumor tissues and is associated with clinicopathological characteristics and prognosis in hepatocellular carcinoma

Cited by 4 publications

References 29 publications

CKAP4 is a potential exosomal biomarker and therapeutic target for lung cancer

CKAP4 is a potential exosomal biomarker and therapeutic target for lung cancer

EGF promotes DKK1 transcription in hepatocellular carcinoma by enhancing the phosphorylation and acetylation of histone H3

Identification of potent novel biomarkers related to Osteoporosis through bioinformatics approach

Contact Info

Product

Resources

About