GABAergic signaling facilitates breast cancer metastasis by promoting ERK1/2-dependent phosphorylation

Zhang, Depu; Li, Xiaowei; Yao, Ziming; Wei, Chen; Ning, Nannan; Li, Jingxin

doi:10.1016/j.canlet.2014.03.006

Cited by 61 publications

(61 citation statements)

References 28 publications

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“…On the other hand, GAD65 is expressed in breast cancer cells and the GABAbR pathway is implicated in breast cancer cell invasion and migration. 44 This observation supports the possibility that GAD may act as a tumor antigen and thus trigger, in some patients, an immune response leading to the development of SPS.…”

Section: Discussionsupporting

confidence: 71%

Paraneoplastic Neurological Syndromes and Glutamic Acid Decarboxylase Antibodies

et al. 2015

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IMPORTANCE Little is known of glutamic acid decarboxylase antibodies (GAD-abs) in the paraneoplastic context. Clinical recognition of such cases will lead to prompt tumor diagnosis and appropriate treatment.OBJECTIVE To report the clinical and immunological features of patients with paraneoplastic neurological syndromes (PNS) and GAD-abs. DESIGN, SETTING, AND PARTICIPANTSRetrospective case series study and immunological investigations conducted in February 2014 in a center for autoimmune neurological disorders. Fifteen cases with GAD65-abs evaluated between 1995 and 2013 who fulfilled criteria of definite or possible PNS without concomitant onconeural antibodies were included in this study. MAIN OUTCOMES AND MEASURESAnalysis of the clinical records of 15 patients and review of 19 previously reported cases. Indirect immunofluorescence with rat hippocampal neuronal cultures and cell-based assays with known neuronal cell-surface antigens were used. One hundred six patients with GAD65-abs and no cancer served as control individuals.RESULTS Eight of the 15 patients with cancer presented as classic paraneoplastic syndromes (5 limbic encephalitis, 1 paraneoplastic encephalomyelitis, 1 paraneoplastic cerebellar degeneration, and 1 opsoclonus-myoclonus syndrome). When compared with the 106 non-PNS cases, those with PNS were older (median age, 60 years vs 48 years; P = .03), more frequently male (60% vs 13%; P < .001), and had more often coexisting neuronal cell-surface antibodies, mainly against γ-aminobutyric acid receptors (53% vs 11%; P < .001). The tumors more frequently involved were lung (n = 6) and thymic neoplasms (n = 4). The risk for an underlying tumor was higher if the presentation was a classic PNS, if it was different from stiff-person syndrome or cerebellar ataxia (odds ratio, 10.5; 95% CI, 3.2-34.5), or if the patient had coexisting neuronal cell-surface antibodies (odds ratio, 6.8; 95% CI, 1.1-40.5). Compared with the current series, the 19 previously reported cases had more frequent stiff-person syndrome (74% vs 13%; P = .001) and better responses to treatment (79% vs 27%; P = .005). Predictors of improvement in the 34 patients (current and previously reported) included presentation with stiff-person syndrome and the presence of a thymic tumor. CONCLUSIONS AND RELEVANCEPatients with GAD-abs must be screened for an underlying cancer if they have clinical presentations different from those typically associated with this autoimmunity or develop classic PNS. The risk for cancer increases with age, male sex, and the presence of coexisting neuronal cell-surface antibodies.

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Section: Discussionsupporting

confidence: 71%

Paraneoplastic Neurological Syndromes and Glutamic Acid Decarboxylase Antibodies

et al. 2015

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“…EGFR phosphorylation can activate several downstream signaling pathways including PI3K/AKT and MAPK/MEK/ERK 16, 35 . MMP-2 is positively regulated by the ERK pathway and regulates degradation of extracellular matrix components, which plays a key role in cancer metastasis 24, 37 . A recent study found that 500 μM NaHS markedly increased MMP-2 expression in human PLC/PRF/5 hepatoma cells 38 .…”

Section: Discussionmentioning

confidence: 99%

Hydrogen sulfide acts as a double-edged sword in human hepatocellular carcinoma cells through EGFR/ERK/MMP-2 and PTEN/AKT signaling pathways

Tian

et al. 2017

Sci Rep

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Hydrogen sulfide (H2S) is involved in cancer biological processes. However, there are several controversies concerning the role of H2S in cancer development and progression. In this study, we found that the growth and migration of hepatocellular carcinoma (HCC) cells were enhanced by 10–100 μM NaHS and dose-dependently inhibited by 600–1000 μM NaHS. The apoptotic levels were reduced by 25–100 μM NaHS but increased by 400–1000 μM NaHS in HCC cells. After treatment with 25–50 μM NaHS, the protein levels of p-EGFR, p-ERK, MMP-2, and p-AKT were increased, whereas the levels of PTEN and the ratio of BAX/BCL-2 were down-regulated. Administration of 800–1000 μM NaHS showed opposite effects on these protein levels in HCC cells. However, H2S showed no effects on the growth, migration, apoptosis, and the protein levels of the EGFR/ERK/MMP-2 and PTEN/AKT signaling pathways in L02 cells. Furthermore, 25–100 μM NaHS promoted HCC tumor growth and blood vessel formation, while 800–1000 μM NaHS inhibited angiogenesis and tumor growth with no obvious systemic toxicity. These results indicate that H2S acts as a double-edged sword in HCC cells through EGFR/ERK/MMP-2 and PTEN/AKT signaling pathways. Novel H2S donors could be designed and applied for further antitumor research.

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“…Gamma‐Aminobutyric acid (GABA) is synthesized predominantly from glutamate by glutamate decarboxylase (GAD) and exerts its effects via ionotropic (GABAA) and metabotropic (GABAB) receptors . Studies have reported that GABA and its receptors could take part in the oncogenesis/metastasis of various carcinomas . However, the results are controversial because GABA might result in the different effects on cancer proliferation/metastasis in a cancer‐type and/or GABA receptor‐type‐dependent manner.…”

Section: Discussionmentioning

confidence: 99%

A distinct serum metabolic signature of distant metastatic papillary thyroid carcinoma

Shen

Zhang

Liu

et al. 2017

Clinical Endocrinology

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Serum metabolomics profiling could significantly discriminate papillary thyroid cancer patients according to distant metastasis. Potential metabolic aberration in distant metastatic PTC could be involved in different biological behaviours of tumour cells including proliferation, invasion/migration and immune escape. Diet/gut microbiota-produced metabolites could play an important role in these effects. This work may provide new clues to find the underlying mechanisms regarding the distant metastasis of PTC as well as potential adjuvant therapy targets.

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GABAergic signaling facilitates breast cancer metastasis by promoting ERK1/2-dependent phosphorylation

Cited by 61 publications

References 28 publications

Paraneoplastic Neurological Syndromes and Glutamic Acid Decarboxylase Antibodies

Paraneoplastic Neurological Syndromes and Glutamic Acid Decarboxylase Antibodies

Hydrogen sulfide acts as a double-edged sword in human hepatocellular carcinoma cells through EGFR/ERK/MMP-2 and PTEN/AKT signaling pathways

A distinct serum metabolic signature of distant metastatic papillary thyroid carcinoma

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