An ADAM12 and FAK positive feedback loop amplifies the interaction signal of tumor cells with extracellular matrix to promote esophageal cancer metastasis

Luo, Man; Zhou, Zhuan; Sun, Lichao; Lan, Yu; Li, Jun; Yang, Zhihua; Ran, Yuliang; Yao, Yihong; Hu, Hai

doi:10.1016/j.canlet.2018.02.031

Cited by 30 publications

(29 citation statements)

References 64 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…ADAM12, also named meltrin‐α, has been reported to be involved in fertilization, muscle development, and cardiac hypertrophy . Recent studies demonstrate ADAM12 is involved in invasion and metastasis of tumor . Kumasawa and colleagues reported that p38 could regulate the expression of ADAM12 in human airway smooth muscle cells .…”

Section: Introductionmentioning

confidence: 99%

“…(21) Recent studies demonstrate ADAM12 is involved in invasion and metastasis of tumor. (22,23) Kumasawa and colleagues reported that p38 could regulate the expression of ADAM12 in human airway smooth muscle cells. (24) ADAM12 is upregulated during the formation of osteoclast, (25)(26)(27) but the function of ADAM12 in osteoclast and the exact mechanism are still unknown.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The Novel p38 Inhibitor, Pamapimod, Inhibits Osteoclastogenesis and Counteracts Estrogen-Dependent Bone Loss in Mice

Zhao

Ning

Xie

et al. 2019

Journal of Bone and Mineral Research

View full text Add to dashboard Cite

Pamapimod (PAM) is a novel selective p38 mitogen‐activated protein (MAP) kinase inhibitor proved to be effective in rheumatoid arthritis in phase 2 clinical trial. However, its effect on osteoclast‐associated osteoporosis and the underlying mechanisms remain unclear. In this study, we showed that PAM suppressed receptor activator of nuclear factor‐κB ligand (RANKL)‐induced osteoclast formation via inhibition of p38 phosphorylation and subsequent c‐Fos and nuclear factor of activated T cells c1 (NFATc1) expression. In addition, the downregulated NFATc1 leads to reduced expression of its targeting gene disintegrin and metalloproteinase domain‐containing protein 12 (ADAM12), which was further proven to be critical for osteoclastic bone resorption. Therefore, we treated ovariectomized (OVX) mice with PAM and revealed a protective effect of PAM on osteoporosis in vivo. In conclusion, our results demonstrated PAM can prevent OVX‐induced bone loss through suppression of p38/NFATc1‐induced osteoclast formation and NFATc1/ADAM12‐associated bone resorption. © 2018 American Society for Bone and Mineral Research.

show abstract

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The Novel p38 Inhibitor, Pamapimod, Inhibits Osteoclastogenesis and Counteracts Estrogen-Dependent Bone Loss in Mice

Zhao

Ning

Xie

et al. 2019

Journal of Bone and Mineral Research

View full text Add to dashboard Cite

show abstract

“…It belongs to a matrix metalloproteinase-related protein family and participates in the proteolytic processing of other transmembrane proteins, with consequences for cell-signalling events, transcription, RNA metabolism, apoptosis, cell-cycle progression, and cell adhesion. ADAM12 overexpression has been reported in many tumours [31,32], especially in BC, where it has been proposed to make an important contribution in carcinogenesis [33][34][35][36]. However, its molecular status in the TNBC subtype is almost entirely unexplored.…”

Section: Discussionmentioning

confidence: 99%

ADAM12 is A Potential Therapeutic Target Regulated by Hypomethylation in Triple-Negative Breast Cancer

Mendaza

Ulazia-Garmendia

Monreal-Santesteban

et al. 2020

IJMS

View full text Add to dashboard Cite

Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype and currently lacks any effective targeted therapy. Since epigenetic alterations are a common event in TNBC, DNA methylation profiling can be useful for identifying potential biomarkers and therapeutic targets. Here, genome-wide DNA methylation from eight TNBC and six non-neoplastic tissues was analysed using Illumina Human Methylation 450K BeadChip. Results were validated by pyrosequencing in an independent cohort of 50 TNBC and 24 non-neoplastic samples, where protein expression was also assessed by immunohistochemistry. The functional role of disintegrin and metalloproteinase domain-containing protein 12(ADAM12) in TNBC cell proliferation, migration and drug response was analysed by gene expression silencing with short hairpin RNA. Three genes (Von Willenbrand factor C and Epidermal Growth Factor domain-containing protein (VWCE), tetraspanin-9 (TSPAN9) and ADAM12) were found to be exclusively hypomethylated in TNBC. Furthermore, ADAM12 hypomethylation was associated with a worse outcome in TNBC tissues and was also found in adjacent-to-tumour tissue and, preliminarily, in plasma from TNBC patients. In addition, ADAM12 silencing decreased TNBC cell proliferation and migration and improved doxorubicin sensitivity in TNBC cells. Our results indicate that ADAM12 is a potential therapeutic target and its hypomethylation could be a poor outcome biomarker in TNBC.

show abstract

“…Esophageal cancer ranks the 6th cancer‐related death in the world . ESCC is a common tissue subtype of esophageal cancer in Asia, including China .…”

Section: Introductionmentioning

confidence: 99%

Targeting the overexpressed USP7 inhibits esophageal squamous cell carcinoma cell growth by inducing NOXA‐mediated apoptosis

Zhang

Sha

et al. 2018

Molecular Carcinogenesis

View full text Add to dashboard Cite

Increasing evidence suggests that deubiquitinase USP7 participates in tumor progression by various mechanisms and serves as a potential therapeutic target. However, its expression and role in esophageal cancer remains elusive; the anti-cancer effect by targeting USP7 still needs to be investigated. Here, we reported that USP7 was overexpressed in esophageal squamous cell carcinoma (ESCC) tissues compared with adjacent tissues, implying that USP7 was an attractive anticancer target of ESCC. Pharmaceutical or genetic inactivation of USP7 inhibited esophageal cancer cells growth in vitro and in vivo and induced apoptosis. Mechanistically, inhibition of USP7 accumulated poly-ubiquitinated proteins, activated endoplasmic reticulum stress, and increased expression of ATF4, which transcriptionally upregulated expression of NOXA and induced NOXA-mediated apoptosis. These results provide an evidence for clinical investigation of USP7 inhibitors for the treatment of ESCC.

show abstract

An ADAM12 and FAK positive feedback loop amplifies the interaction signal of tumor cells with extracellular matrix to promote esophageal cancer metastasis

Cited by 30 publications

References 64 publications

The Novel p38 Inhibitor, Pamapimod, Inhibits Osteoclastogenesis and Counteracts Estrogen-Dependent Bone Loss in Mice

The Novel p38 Inhibitor, Pamapimod, Inhibits Osteoclastogenesis and Counteracts Estrogen-Dependent Bone Loss in Mice

ADAM12 is A Potential Therapeutic Target Regulated by Hypomethylation in Triple-Negative Breast Cancer

Targeting the overexpressed USP7 inhibits esophageal squamous cell carcinoma cell growth by inducing NOXA‐mediated apoptosis

Contact Info

Product

Resources

About