Afamin promotes glucose metabolism in papillary thyroid carcinoma

Shen, Ce; Wei, Weijun; Qiu, Zhong-Ling; Song, Hong-Jun; Luo, Quan-Yong

doi:10.1016/j.mce.2016.06.013

Cited by 21 publications

(17 citation statements)

References 37 publications

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“…Tumorigenesis and tumor development depend on the reprogramming of tumor metabolism [ 3 , 4 ] to a certain extent. Targeting reprogramming of tumor metabolism may ultimately contribute to better directing tumor therapy [ 5 , 6 , 7 ].…”

Section: Introductionmentioning

confidence: 99%

Effects of targeting SLC1A5 on inhibiting gastric cancer growth and tumor development in vitro and in vivo

et al. 2017

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AimsTo investigate the oncogenic effects of SLC1A5 on gastric cancer development in vitro and in vivo.MethodsThe expression level of SLC1A5 was detected in 70 gastric cancer paraffin-embedded tissues by immunohistochemistry and also was detected in gastric cancer cell lines by qRT-PCR and western blotting analysis. The effects of knockdown SLC1A5 were analyzed on cell proliferation, cell cycle, the ability of cell migration and invasion and growth signaling pathway in vitro. By using subcutaneous xenograft mouse, the importance of SLC1A5 expression was assessed for both successful engraftment and growth of gastric cancer cells in vivo.ResultsSLC1A5 was up-regulated in gastric cancer tissues and was correlated with malignant features such as deeper local invasion, higher lymph node metastasis, advanced TNM stages and higher Ki-67 expression. Knockdown SLC1A5 in gastric cancer cells suppressed cell proliferation, caused G0/G1 arrest and inhibited cell invasion as well as migration partly by inactivated mTOR/p-70S6K1 signaling pathway in vitro. Furthermore, in vivo experiments indicated that suppression of SLC1A5 could inhibit relative volume of xenografted tumor.ConclusionsOur results suggested that SLC1A5 might be considered as a new biomarker and also as a potential therapeutic target in gastric cancer.

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Section: Introductionmentioning

confidence: 99%

Effects of targeting SLC1A5 on inhibiting gastric cancer growth and tumor development in vitro and in vivo

et al. 2017

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“…N14 serves as the detection antibody in afamin ELISAs (Dieplinger et al, 2013), and its Fab antibody fragment can be used for crystallization scaffolding experiments of the complex glycosylated human plasma protein afamin, which is a promiscuous transporter of hydrophobic molecules, including vitamin E (Voegele et al, 2002). Afamin may also play a role in the Wnt signalling pathway or serve as a chaperone enhancing the solubility of Wnt proteins (Mihara et al, 2016) and has a potential role in glucose metabolism in papillary thyroid carcinoma (Shen et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

“…Strong interest in the AFM crystal structure results from the fact that it seems to be, at least in vitro, a carrier for Wnt signalling proteins (which are relevant in cell proliferation pathways), which are otherwise very hard to solubilize and to purify (Mihara et al, 2016). A potential role of afamin in the glucose metabolism in papillary thyroid carcinoma has been reported (Shen et al, 2016), and the N14 Fab (fragment, antigen binding) can serve as a scaffolding partner in AFM crystallization. The N14 Fab displays a number of interesting structural features and its crystallization in two crystal forms with non-apparent isomorphism also allows an extended analysis of its structural flexibility and of the practice and effects of extensive solvent model building.…”

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confidence: 99%

The N14 anti-afamin antibody Fab: a rare V_L1 CDR glycosylation, crystallographic re-sequencing, molecular plasticity and conservativeversusenthusiastic modelling

Naschberger

Fürnrohr

Roviš

et al. 2016

Acta Cryst Sect D Struct Biol

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“…Western blotting was carried out as described previously 15, 21, 22. Anti-Bcl-2, anti-Mcl-1, anti-PARP1, anti-cytochrome C, anti-ERK, anti-p-ERK, anti-Bim, anti-TSHR, anti-HK2, anti-Bax, anti-cyclin D1, and anti-GAPDH antibodies were purchased from ProteinTech (Chicago, IL, USA); anti-GLUT1 (NB110-39113SS) antibody was acquired from Novusbio.…”

Section: Methodsmentioning

confidence: 99%

Obatoclax and LY3009120 Efficiently Overcome Vemurafenib Resistance in Differentiated Thyroid Cancer

Wei¹,

Sun²,

Shen³

et al. 2017

Theranostics

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Although the prognosis of differentiated thyroid cancer (DTC) is relatively good, 30-40% of patients with distant metastases develop resistance to radioactive iodine therapy due to tumor dedifferentiation. For DTC patients harboring BRAFV600E mutation, Vemurafenib, a BRAF kinase inhibitor, has dramatically changed the therapeutic landscape, but side effects and drug resistance often lead to termination of the single agent treatment. In the present study, we showed that either LY3009120 or Obatoclax (GX15-070) efficiently inhibited cell cycle progression and induced massive death of DTC cells. We established that BRAF/CRAF dimerization was an underlying mechanism for Vemurafenib resistance. LY3009120, the newly discovered pan-RAF inhibitor, successfully overcame Vemurafenib resistance and suppressed the growth of DTC cells in vitro and in vivo. We also observed that expression of anti-apoptotic Bcl-2 increased substantially following BRAF inhibitor treatment in Vemurafenib-resistant K1 cells, and both Obatoclax and LY3009120 efficiently induced apoptosis of these resistant cells. Specifically, Obatoclax exerted its anti-cancer activity by inducing loss of mitochondrial membrane potential (ΔΨm), dysfunction of mitochondrial respiration, reduction of cellular glycolysis, autophagy, neutralization of lysosomes, and caspase-related apoptosis. Furthermore, the cancer killing effects of LY3009120 and Obatoclax extended to two more Vemurafenib-resistant DTC cell lines, KTC-1 and BCPAP. Taken together, our results highlighted the potential value of LY3009120 for both Vemurafenib-sensitive and -resistant DTC and provided evidence for the combination therapy using Vemurafenib and Obatoclax for radioiodine-refractory DTC.

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Afamin promotes glucose metabolism in papillary thyroid carcinoma

Cited by 21 publications

References 37 publications

Effects of targeting SLC1A5 on inhibiting gastric cancer growth and tumor development in vitro and in vivo

Effects of targeting SLC1A5 on inhibiting gastric cancer growth and tumor development in vitro and in vivo

The N14 anti-afamin antibody Fab: a rare V_L1 CDR glycosylation, crystallographic re-sequencing, molecular plasticity and conservativeversusenthusiastic modelling

Obatoclax and LY3009120 Efficiently Overcome Vemurafenib Resistance in Differentiated Thyroid Cancer

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Afamin promotes glucose metabolism in papillary thyroid carcinoma

Cited by 21 publications

References 37 publications

Effects of targeting SLC1A5 on inhibiting gastric cancer growth and tumor development in vitro and in vivo

Effects of targeting SLC1A5 on inhibiting gastric cancer growth and tumor development in vitro and in vivo

The N14 anti-afamin antibody Fab: a rare VL1 CDR glycosylation, crystallographic re-sequencing, molecular plasticity and conservativeversusenthusiastic modelling

Obatoclax and LY3009120 Efficiently Overcome Vemurafenib Resistance in Differentiated Thyroid Cancer

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About

The N14 anti-afamin antibody Fab: a rare V_L1 CDR glycosylation, crystallographic re-sequencing, molecular plasticity and conservativeversusenthusiastic modelling