ATP11B inhibits breast cancer metastasis in a mouse model by suppressing externalization of nonapoptotic phosphatidylserine

Xu, Jun; Su, Sek Man; Zhang, Xin; Chan, Un In; Adhav, Ragini; Shu, Xiaodong; Liu, Jianlin; Li, Jianjie; Mo, Li‐Hua; Wang, Yuqing; An, Tingting; Lei, Josh Haipeng; Kai, Masahiro; Deng, Chu‐Xia; Xu, Xiaoling

doi:10.1172/jci149473

Cited by 11 publications

(5 citation statements)

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“…RNA pull-down and mass spectrometry were performed to explore potential protein binding partners, and we screened 18 bindings proteins (unique peptide number > 8, PG coverage > 25%) as candidates for LINC00606 to exert tumor regulatory mechanisms in the GBM (Supplementary Table S 7 ). Previous studies have shown that the candidate protein ATP11B is an inhibitor of cancer metastasis [ 40 ] and displays heterogeneous expression in various nerve cell-s in the brain [ 24 ]. ATP11B is closely related to the field of neurology or oncology, so we selected ATP11B as the binding protein for our research.…”

Section: Resultsmentioning

confidence: 99%

“…Previous studies have shown that the candidate protein ATP11B is an inhibitor of cancer metastasis [40] and displays heterogeneous expression in various nerve cells in the brain [24]. ATP11B is closely related to the field of neurology or oncology, so we selected ATP11B as the binding protein for our research.…”

Section: Linc00606 Regulates Carcinogenesis By Cooperating With Atp11...mentioning

confidence: 99%

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LINC00606 promotes glioblastoma progression through sponge miR-486-3p and interaction with ATP11B

Dong,

Qi,

et al. 2024

J Exp Clin Cancer Res

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Background LncRNAs regulate tumorigenesis and development in a variety of cancers. We substantiate for the first time that LINC00606 is considerably expressed in glioblastoma (GBM) patient specimens and is linked with adverse prognosis. This suggests that LINC00606 may have the potential to regulate glioma genesis and progression, and that the biological functions and molecular mechanisms of LINC00606 in GBM remain largely unknown. Methods The expression of LINC00606 and ATP11B in glioma and normal brain tissues was evaluated by qPCR, and the biological functions of the LINC00606/miR-486-3p/TCF12/ATP11B axis in GBM were verified through a series of in vitro and in vivo experiments. The molecular mechanism of LINC00606 was elucidated by immunoblotting, FISH, RNA pulldown, CHIP-qPCR, and a dual-luciferase reporter assay. Results We demonstrated that LINC00606 promotes glioma cell proliferation, clonal expansion and migration, while reducing apoptosis levels. Mechanistically, on the one hand, LINC00606 can sponge miR-486-3p; the target gene TCF12 of miR-486-3p affects the transcriptional initiation of LINC00606, PTEN and KLLN. On the other hand, it can also regulate the PI3K/AKT signaling pathway to mediate glioma cell proliferation, migration and apoptosis by binding to ATP11B protein. Conclusions Overall, the LINC00606/miR-486-3p/TCF12/ATP11B axis is involved in the regulation of GBM progression and plays a role in tumor regulation at transcriptional and post-transcriptional levels primarily through LINC00606 sponging miR-486-3p and targeted binding to ATP11B. Therefore, our research on the regulatory network LINC00606 could be a novel therapeutic strategy for the treatment of GBM. Graphical Abstract LINC00606 is highly expressed in GBM patients with carcinogenic function and correlated with poor prognosis. LINC00606 regulates glioblastoma progression by sponging miR-486-3p and interacting with ATP11B.

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Section: Resultsmentioning

confidence: 99%

Section: Linc00606 Regulates Carcinogenesis By Cooperating With Atp11...mentioning

confidence: 99%

LINC00606 promotes glioblastoma progression through sponge miR-486-3p and interaction with ATP11B

Dong,

Qi,

et al. 2024

J Exp Clin Cancer Res

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“…Anionic phospholipids, principally PS, are specifically exposed on tumor endothelial cells, possibly in response to oxidative stresses present in the tumor microenvironment [ 22 , 23 ]. Although enhanced PS externalization in cancer is widely accepted, the exact mechanism remains unclear [ 24 ]. Tumor cells and tumor vasculature alter their total phospholipid concentrations, have more PS in the plasma membrane, and have up to sevenfold more externalized PS than healthy cells [ 1 ].…”

Section: Discussionmentioning

confidence: 99%

Integrin Targeting Enhances the Antimelanoma Effect of Annexin V in Mice

Zhu

Gao

et al. 2023

IJMS

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Malignant melanoma, an increasingly common form of skin cancer, is a major threat to public health, especially when the disease progresses past skin lesions to the stage of advanced metastasis. Targeted drug development is an effective strategy for the treatment of malignant melanoma. In this work, a new antimelanoma tumor peptide, the lebestatin–annexin V (designated LbtA5) fusion protein, was developed and synthesized by recombinant DNA techniques. As a control, annexin V (designated ANV) was also synthesized by the same method. The fusion protein combines annexin V, which specifically recognizes and binds phosphatidylserine, with the disintegrin lebestatin (lbt), a polypeptide that specifically recognizes and binds integrin α1β1. LbtA5 was successfully prepared with good stability and high purity while retaining the dual biological activity of ANV and lbt. MTT assays demonstrated that both ANV and LbtA5 could reduce the viability of melanoma B16F10 cells, but the activity of the fusion protein LbtA5 was superior to that of ANV. The tumor volume growth was slowed in a mouse xenograft model treated with ANV and LbtA5, and the inhibitory effect of high concentrations of LbtA5 was significantly better than that of the same dose of ANV and was comparable to that of DTIC, a drug used clinically for melanoma treatment. The hematoxylin and eosin (H&E) staining test showed that ANV and LbtA5 had antitumor effects, but LbtA5 showed a stronger ability to induce melanoma necrosis in mice. Immunohistochemical experiments further showed that ANV and LbtA5 may inhibit tumor growth by inhibiting angiogenesis in tumor tissue. Fluorescence labeling experiments showed that the fusion of ANV with lbt enhanced the targeting of LbtA5 to mouse melanoma tumor tissue, and the amount of target protein in tumor tissue was significantly increased. In conclusion, effective coupling of the integrin α1β1-specific recognition molecule lbt confers stronger biological antimelanoma effects of ANV, which may be achieved by the dual effects of effective inhibition of B16F10 melanoma cell viability and inhibition of tumor tissue angiogenesis. The present study describes a new potential strategy for the application of the promising recombinant fusion protein LbtA5 in the treatment of various cancers, including malignant melanoma.

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“…LncRNAs typically bind directly to proteins to regulate the occurrence and development of disease [30]. Previous studies have shown that ATP11B is an inhibitor of cancer metastasis [31] and displays heterogeneous expression in various nerve cells in the brain [32]. We used the catRAPID website to predict the binding relationship between LINC00606 and ATP11B, uncovering that both these proteins possess RNA binding domains (Supplementary Fig.…”

Section: Linc00606 Regulates Carcinogenesis By Cooperating With Atp11...mentioning

confidence: 99%

LINC00606 regulates glioblastoma progression by sponging miR-486-3p and interacting with ATP11B

Dong

et al. 2023

Preprint

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Background LncRNAs regulate tumorigenesis and development in a variety of cancers; nevertheless, the biological functions and molecular mechanisms of LINC00606 in glioblastoma (GBM) remain largely unknown. Methods The expression of LINC00606 and ATP11B in glioma and normal brain tissues was evaluated by qPCR, and the biological functions of the LINC00606/miR-486-3p/TCF12/ATP11B axis in GBM were verified through a series of in vitro and in vivoexperiments. The molecular mechanism of LINC00606 was revealed by immunoblotting, FISH, RNA pulldown, CHIP-qPCR, and a dual-luciferase reporter assay. Results LINC00606 is highly expressed in GBM patient samples and is related to the poor prognosis. Here, LINC00606 promoted the proliferation, clonal expansion, and migration of glioma cells and reduced the levels of apoptosis. LINC00606 targets TCF12 by sponging miR-486-3p, which has been proven to affect the transcriptional initiation of LINC00606, PTEN, and KLLN. In addition, by working in concert with ATP11B, LINC00606 regulates the PI3K/AKT signaling pathway to mediate the proliferation, migration, and apoptosis of glioma cells. Conclusion The LINC00606/miR-486-3p/TCF12/ATP11B axis is involved in the regulation of glioma progression and plays a specific regulatory role at both the transcriptional and post-transcriptional levels via the sponging of miR-486-3p by LINC00606 to target TCF12 and the interaction of LINC00606 with ATP11B, interference with which may prove to be a new strategy for the treatment of glioblastoma.

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ATP11B inhibits breast cancer metastasis in a mouse model by suppressing externalization of nonapoptotic phosphatidylserine

Cited by 11 publications

References 47 publications

LINC00606 promotes glioblastoma progression through sponge miR-486-3p and interaction with ATP11B

LINC00606 promotes glioblastoma progression through sponge miR-486-3p and interaction with ATP11B

Integrin Targeting Enhances the Antimelanoma Effect of Annexin V in Mice

LINC00606 regulates glioblastoma progression by sponging miR-486-3p and interacting with ATP11B

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