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  • 1
    Online Resource
    Online Resource
    Ivyspring International Publisher ; 2020
    In:  International Journal of Medical Sciences Vol. 17, No. 17 ( 2020), p. 2773-2789
    In: International Journal of Medical Sciences, Ivyspring International Publisher, Vol. 17, No. 17 ( 2020), p. 2773-2789
    Type of Medium: Online Resource
    ISSN: 1449-1907
    Language: English
    Publisher: Ivyspring International Publisher
    Publication Date: 2020
    detail.hit.zdb_id: 2151424-0
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  • 2
    In: eLife, eLife Sciences Publications, Ltd, Vol. 11 ( 2022-03-14)
    Abstract: Integrin family are known as key gears in focal adhesion for triple-negative breast cancer (TNBC) metastasis. However, the integrin independent factor TLN1 remains vague in TNBC. Methods: Bioinformatics analysis was performed based on TCGA database and Shengjing Hospital cohort. Western blot and RT-PCR were used to detect the expression of TLN1 and integrin pathway in cells. A small-molecule C67399 was screened for blocking TLN1 and integrin β1 through a novel computational screening approach by targeting the protein-protein binding interface. Drug pharmacodynamics were determined through xenograft assay. Results: Upregulation of TLN1 in TNBC samples correlates with metastasis and worse prognosis. Silencing TLN1 in TNBC cells significantly attenuated the migration of tumour cells through interfering the dynamic formation of focal adhesion with integrin β1, thus regulating FAK-AKT signal pathway and epithelial-mesenchymal transformation. Targeting the binding between TLN1 and integrin β1 by C67399 could repress metastasis of TNBC. Conclusions: TLN1 overexpression contributes to TNBC metastasis and C67399 targeting TLN1 may hold promise for TNBC treatment. Funding: This study was supported by grants from the National Natural Science Foundation of China (No. 81872159, 81902607, 81874301), Liaoning Colleges Innovative Talent Support Program (Name: Cancer Stem Cell Origin and Biological Behaviour), Outstanding Scientific Fund of Shengjing Hospital (201803), and Outstanding Young Scholars of Liaoning Province (2019-YQ-10).
    Type of Medium: Online Resource
    ISSN: 2050-084X
    Language: English
    Publisher: eLife Sciences Publications, Ltd
    Publication Date: 2022
    detail.hit.zdb_id: 2687154-3
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  • 3
    Online Resource
    Online Resource
    Ivyspring International Publisher ; 2020
    In:  International Journal of Medical Sciences Vol. 17, No. 17 ( 2020), p. 2819-2825
    In: International Journal of Medical Sciences, Ivyspring International Publisher, Vol. 17, No. 17 ( 2020), p. 2819-2825
    Type of Medium: Online Resource
    ISSN: 1449-1907
    Language: English
    Publisher: Ivyspring International Publisher
    Publication Date: 2020
    detail.hit.zdb_id: 2151424-0
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  • 4
    In: Nature Communications, Springer Science and Business Media LLC, Vol. 14, No. 1 ( 2023-05-05)
    Abstract: Failure to achieve complete elimination of triple negative breast cancer (TNBC) stem cells after adjuvant therapy is associated with poor outcomes. Aldehyde dehydrogenase 1 (ALDH1) is a marker of breast cancer stem cells (BCSCs), and its enzymatic activity regulates tumor stemness. Identifying upstream targets to control ALDH + cells may facilitate TNBC tumor suppression. Here, we show that KK-LC-1 determines the stemness of TNBC ALDH + cells via binding with FAT1 and subsequently promoting its ubiquitination and degradation. This compromises the Hippo pathway and leads to nuclear translocation of YAP1 and ALDH1A1 transcription. These findings identify the KK-LC-1-FAT1-Hippo-ALDH1A1 pathway in TNBC ALDH + cells as a therapeutic target. To reverse the malignancy due to KK-LC-1 expression, we employ a computational approach and discover Z839878730 (Z8) as an small-molecule inhibitor which may disrupt KK-LC-1 and FAT1 binding. We demonstrate that Z8 suppresses TNBC tumor growth via a mechanism that reactivates the Hippo pathway and decreases TNBC ALDH + cell stemness and viability.
    Type of Medium: Online Resource
    ISSN: 2041-1723
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 2553671-0
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  • 5
    Online Resource
    Online Resource
    Wiley ; 2020
    In:  Journal of Cellular and Molecular Medicine Vol. 24, No. 16 ( 2020-08), p. 9125-9134
    In: Journal of Cellular and Molecular Medicine, Wiley, Vol. 24, No. 16 ( 2020-08), p. 9125-9134
    Abstract: Lipase member H (LIPH), a novel member of the triglyceride lipase family. The clinical implications of its expression in breast cancer are still unclear. Therefore, in this study, we investigated the associations between LIPH and the tumorigenic behaviours of 144 triple‐negative breast cancer (TNBC) patients. The ratio and mammosphere‐forming ability of CD44+/CD24− stem‐like cells were tested. The role of LIPH in breast cancer cell migration and invasion was also evaluated. In addition, the effect of LIPH silencing on mitochondrial respiration was determined using the Seahorse assay. Finally, the effect of LIPH silencing on protein expression was determined via tandem mass tag‐based spectrometry and Western blotting. We found that LIPH expression was associated with metastasis in lymph nodes and distant organs ( P  = 0.025), resulting in poor survival among breast cancer patients ( P  = 0.027). LIPH knockdown significantly decreased both the ratio of CD44 + /CD24 − stem‐like cells and their mammosphere‐forming ability. LIPH silencing promoted apoptosis, arrested cell cycle in the G2/M phase, mitigated the oxidation‐related oxygen consumption rate in the mitochondria, and reduced metabolism. LIPH inhibited adhesion between tumour cells and enhanced the epithelial‐mesenchymal transition. Tandem mass spectrometric analysis presented 68 proteins were differentially expressed in LIPH‐silenced cells and LIPH‐mediated modulation of tumour cell adhesion depended on integrin‐related CAPN2 and paxillin signalling. Overall, our findings provided strong evidence that LIPH up‐regulation promoted metastasis and the stemness of TNBC cells. Therefore, targeting LIPH is a potentially viable strategy for preventing metastasis in TNBC.
    Type of Medium: Online Resource
    ISSN: 1582-1838 , 1582-4934
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2020
    detail.hit.zdb_id: 2076114-4
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  • 6
    Online Resource
    Online Resource
    Wiley ; 2018
    In:  Annals of the New York Academy of Sciences Vol. 1433, No. 1 ( 2018-12), p. 53-60
    In: Annals of the New York Academy of Sciences, Wiley, Vol. 1433, No. 1 ( 2018-12), p. 53-60
    Abstract: Staphylococcal nuclease domain‐containing 1 (SND1) expression is crucial for breast cancer metastasis; however, the clinical implications of SND1 expression in breast cancer remain unclear. This study investigated the relationship of SND1 protein expression both with metastasis and the prognoses of 144 breast cancer patients over a 10‐year follow‐up. Chi‐square tests revealed that the percentages of positive SND1 expression in breast cancer tumors were significantly associated with larger tumor size ( 〉 2 cm, P = 0.043), higher clinical TNM stage ( P = 0.003), and positive lymph node metastasis ( P = 0.001). Breast cancer patients with positive SND1 expression had a significantly shorter overall survival and disease‐free survival than those with negative SND1 expression ( P 〈  0.01). Multiple Cox regression analysis indicated that SND1 expression is an independent risk factor for shorter disease‐free survival (hazard ratio = 1.97, P = 0.014). The percentages of SND1 expression in metastatic breast cancers were significantly higher than that in primary tumors in 30 patients with advanced breast cancer ( P = 0.016). Therefore, SND1 protein expression is significantly associated with breast cancer metastasis and may serve as a biomarker for prognosis of breast cancer patients.
    Type of Medium: Online Resource
    ISSN: 0077-8923 , 1749-6632
    URL: Issue
    RVK:
    Language: English
    Publisher: Wiley
    Publication Date: 2018
    detail.hit.zdb_id: 2834079-6
    detail.hit.zdb_id: 211003-9
    detail.hit.zdb_id: 2071584-5
    SSG: 11
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  • 7
    Online Resource
    Online Resource
    Ivyspring International Publisher ; 2022
    In:  International Journal of Medical Sciences Vol. 19, No. 3 ( 2022), p. 434-445
    In: International Journal of Medical Sciences, Ivyspring International Publisher, Vol. 19, No. 3 ( 2022), p. 434-445
    Type of Medium: Online Resource
    ISSN: 1449-1907
    Language: English
    Publisher: Ivyspring International Publisher
    Publication Date: 2022
    detail.hit.zdb_id: 2151424-0
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  • 8
    Online Resource
    Online Resource
    Ovid Technologies (Wolters Kluwer Health) ; 2019
    In:  Annals of Plastic Surgery Vol. 83, No. 4 ( 2019-10), p. 396-400
    In: Annals of Plastic Surgery, Ovid Technologies (Wolters Kluwer Health), Vol. 83, No. 4 ( 2019-10), p. 396-400
    Abstract: This study aimed to compare breast symmetry and patient satisfaction with breast appearance between implant-based breast reconstruction using TiLoop Bra mesh combined with pectoralis major disconnection (IMR) and conventional implant reconstruction (IR), and to analyze differences in complications. Methods This retrospective study included 59 patients administered IMR or IR in 2016 to 2018. Three-dimensional scanning was performed to objectively evaluate breast symmetry. The BREAST-Q scale was used to survey satisfaction with breast appearance, social psychosocial health, physical health, and sexual well-being. Results There were no significant differences in age, TNM stage, and chemotherapy between the 2 groups (all P 〉 0.05). In 3-dimensional scanning data, patients who underwent IMR had better bilateral breast symmetry compared with those administered IR (all P 〈 0.001). Based on the BREAST-Q survey, the satisfaction rate was significantly higher for IMR compared with IR ( P = 0.0368), whereas psychosocial health, physical health, and sexual well-being showed no significant differences between the 2 groups (all P 〉 0.05). The IMR model showed no obvious advantages in common complications, including hematoma, incision site infection, skin flap necrosis, and prosthesis exposure and rupture compared with IR; loss of skin and nipple sensations was evident in both groups. The IMR model was associated with reduced incidence of fibrous capsule contracture compared with IR (0% vs 18.75%, P = 0.0267). The incidence rates of pectoralis major disconnection syndrome after IMR and IR were 18.50% and 0%, respectively ( P = 0.0161). Conclusions Patients administered IMR have better breast symmetry and greater satisfaction with breast appearance compared with those treated by IR; however, IMR has unique complications, including pectoralis major disconnection syndrome.
    Type of Medium: Online Resource
    ISSN: 1536-3708 , 0148-7043
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2019
    detail.hit.zdb_id: 2063013-X
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  • 9
    In: Molecular Cancer, Springer Science and Business Media LLC, Vol. 21, No. 1 ( 2022-12-29)
    Abstract: Breast cancer metastasis to the bone can be exacerbated by osteoporosis, is associated with poor long-term survival, and has limited therapeutic options. Sclerostin (SOST) is an endogenous inhibitor of bone formation, and an attractive target for treatment of osteoporosis. However, it is unclear whether SOST can be used as a therapeutic target for bone metastases of breast cancer, and whether small molecule compounds that target SOST in breast cancer cells can inhibit breast cancer bone metastasis. Methods SOST expression in 442 breast cancer tissues was characterized by immunohistochemistry and statistically analyzed for the association with breast cancer bone metastases. Bone metastatic breast cancer SCP2 cells were induced for SOST silencing or overexpression and their bone metastatic behaviors were tested in vitro and in vivo. To identify potential therapeutics, we screened inhibitors of the interaction of SOST with STAT3 from a small chemical molecule library and tested the inhibitory effects of one inhibitor on breast cancer growth and bone metastasis in vitro and in vivo. Results We found that up-regulated SOST expression was associated with breast cancer bone metastases and worse survival of breast cancer patients. SOST silencing significantly reduced the bone metastatic capacity of SCP2 cells. SOST interacted with STAT3 to enhance the TGF-β/KRAS signaling, increasing both tumor growth and bone metastasis. Treatment with one lead candidate, S6, significantly inhibited the growth of breast-cancer organoids and bone metastasis in mice. Conclusions Our findings highlight a new class of potential therapeutics for treatment of bone metastasis in breast cancer.
    Type of Medium: Online Resource
    ISSN: 1476-4598
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2091373-4
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  • 10
    Online Resource
    Online Resource
    Ivyspring International Publisher ; 2021
    In:  International Journal of Medical Sciences Vol. 18, No. 1 ( 2021), p. 239-244
    In: International Journal of Medical Sciences, Ivyspring International Publisher, Vol. 18, No. 1 ( 2021), p. 239-244
    Type of Medium: Online Resource
    ISSN: 1449-1907
    Language: English
    Publisher: Ivyspring International Publisher
    Publication Date: 2021
    detail.hit.zdb_id: 2151424-0
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