Valosin‑containing protein promotes metastasis of osteosarcoma through autophagy induction and anoikis inhibition via the ERK/NF‑κβ/beclin‑1 signaling pathway

Long, Xin; Zhou, Yanzhao; Lan, Min; Huang, Shan; Liu, Zhi Li; Shu, Yongqian

doi:10.3892/ol.2019.10716

Cited by 7 publications

(6 citation statements)

References 43 publications

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“…Thus, approaches targeting the VCP/miR-129-5p signaling pathway might represent a therapeutic strategy for osteosarcoma management [ 93 ]. Moreover, the authors of a recent study modulated VCP/p97 expression and observed a connection with autophagy induction, anoikis resistance and osteosarcoma cell metastasis [ 94 ]. An interesting study assessing Saos-2 osteosarcoma cells highlighted a novel regulatory mechanism mediated by the serum amyloid p (SAP) protein, an apoptotic inducer that binds to VCP/p97, precluding it from exerting an anti-apoptotic effect [ 95 ].…”

Section: Vcp/p97 Expression and Function In Cancermentioning

confidence: 99%

Valosin-Containing Protein (VCP)/p97: A Prognostic Biomarker and Therapeutic Target in Cancer

Costantini

Capone

Polo

et al. 2021

IJMS

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Valosin-containing protein (VCP)/p97, a member of the AAA+ ATPase family, is a molecular chaperone recruited to the endoplasmic reticulum (ER) membrane by binding to membrane adapters (nuclear protein localization protein 4 (NPL4), p47 and ubiquitin regulatory X (UBX) domain-containing protein 1 (UBXD1)), where it is involved in ER-associated protein degradation (ERAD). However, VCP/p97 interacts with many cofactors to participate in different cellular processes that are critical for cancer cell survival and aggressiveness. Indeed, VCP/p97 is reported to be overexpressed in many cancer types and is considered a potential cancer biomarker and therapeutic target. This review summarizes the role of VCP/p97 in different cancers and the advances in the discovery of small-molecule inhibitors with therapeutic potential, focusing on the challenges associated with cancer-related VCP mutations in the mechanisms of resistance to inhibitors.

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Section: Vcp/p97 Expression and Function In Cancermentioning

confidence: 99%

Valosin-Containing Protein (VCP)/p97: A Prognostic Biomarker and Therapeutic Target in Cancer

Costantini

Capone

Polo

et al. 2021

IJMS

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“…Inhibition of VCP expression may suppress OS metastasis by modulating the PI3K/NF-κβ signaling pathway (19). However, our previous study revealed that inhibition of the PI3K/NF-κβ pathway does not completely reverse VCP-mediated invasion and migration of OS (Long et al, unpublished The further study found that VCP could induces autophagy and inhibits anoikis to promote osteosarcoma metastasis [30]. But the level of autophagy has no effect on the invasion and metastasis ability of OS cells, which suggests that other mechanisms of VCP-mediated OS invasion and migration may be involved.…”

Section: Discussionmentioning

confidence: 92%

Studies on a novel mechanisms of VCP-mediated metastasis of osteosarcoma based on cell autophagy and EMT pathway

Zhang

Fan³

et al. 2022

Preprint

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Objective: Study of the molecular mechanisms of metastasis is still the research focus for osteosarcoma(OS) prevention. This study is to explore a new way for VCP promoting OS metastasis from the perspective of autophagy and epithelial-mesenchymal transition (EMT) in vitro.Method: Different cell lines of osteosarcoma (143B and MG63) were adopted in this study. Gene interference technology was used to down-regulate the expression of VCP, and the expression levels of autophagy and EMT-related protein in OS cells were detect by western blot, as well as smad pathway related protein. Then the process of autophagy and EMT in OS cells were changed artificially, and the cells phenotype were detected respectively. Result: The expression of the LC3II/I was decreased but the insolubilized P62 protein expression was increased in VCP inhibiting group, as well as that in autophagy inhibitor treatment group, which suggesting the down-regulation of the autophagy level of OS cells. At the same time, the expression of the E-cadherin protein was incresed but the N-cadherin was decreased which suggesting the down-regulation of the EMT level in VCP inhibiting group, contrarily that in TGF-β1 treatment group. In addition, suppressing VCP can cause a decrease of Transforming Growth Factor β1（TGF-β1）, smad2, smad3, phosphorylated smad2（p-smad2） and phosphorylated smad3（p-smad3）. Autophagy inhibitors and agonists has no significant effect on the migration and invasion of OS cells, but can significantly affect the ability of cells to resist anoikis. EMT inhibitors and agonists has a proportional effect on the migration and invasion of OS cells.Conclusion: VCP is likely to promote the migration and invasion of OS cells by inducing EMT possibly via TGF-β1/Smad2/3 signaling pathway, and VCP-mediated autophagy plays a key role in this process, contributing to the successful distant metastasis of tumor cells.

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“…However, although stromal cells produce over 90% of the ECM mass [30], it was demonstrated that proteins of the ECM are highly expressed in pancreatic cancer cells [31] and elevated levels of ECM proteins derived from tumor cells of pancreatic cancer, but not those produced exclusively by stromal cells, tend to correlate with poor patient survival in pancreatic cancer [30]. The identified proteins are involved in cell migration (Collagen alpha-2(I) chain) [32], effected cancer cell motility (Actin) [33], promotion of metastasis (Valosin-containing protein) [34], cancer cell viability, angiogenesis (Collagen alpha-3(VI) chain) [35] and tumor progression (Collagen alpha-2(I) chain) [36].…”

Section: Discussionmentioning

confidence: 99%

Peptide Signatures for Prognostic Markers of Pancreatic Cancer by MALDI Mass Spectrometry Imaging

Loch

Klein

Beyer

et al. 2021

Biology

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Despite the overall poor prognosis of pancreatic cancer there is heterogeneity in clinical courses of tumors not assessed by conventional risk stratification. This yields the need of additional markers for proper assessment of prognosis and multimodal clinical management. We provide a proof of concept study evaluating the feasibility of Matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) to identify specific peptide signatures linked to prognostic parameters of pancreatic cancer. On 18 patients with exocrine pancreatic cancer after tumor resection, MALDI imaging analysis was performed additional to histopathological assessment. Principal component analysis (PCA) was used to explore discrimination of peptide signatures of prognostic histopathological features and receiver operator characteristic (ROC) to identify which specific m/z values are the most discriminative between the prognostic subgroups of patients. Out of 557 aligned m/z values discriminate peptide signatures for the prognostic histopathological features lymphatic vessel invasion (pL, 16 m/z values, eight proteins), nodal metastasis (pN, two m/z values, one protein) and angioinvasion (pV, 4 m/z values, two proteins) were identified. These results yield proof of concept that MALDI-MSI of pancreatic cancer tissue is feasible to identify peptide signatures of prognostic relevance and can augment risk assessment.

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Valosin‑containing protein promotes metastasis of osteosarcoma through autophagy induction and anoikis inhibition via the ERK/NF‑κβ/beclin‑1 signaling pathway

Cited by 7 publications

References 43 publications

Valosin-Containing Protein (VCP)/p97: A Prognostic Biomarker and Therapeutic Target in Cancer

Valosin-Containing Protein (VCP)/p97: A Prognostic Biomarker and Therapeutic Target in Cancer

Studies on a novel mechanisms of VCP-mediated metastasis of osteosarcoma based on cell autophagy and EMT pathway

Peptide Signatures for Prognostic Markers of Pancreatic Cancer by MALDI Mass Spectrometry Imaging

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