The wnt/β‐catenin signaling pathway: A potential therapeutic target in the treatment of triple negative breast cancer

King, Taj D.; Suto, Mark J.; Li, Yonghe

doi:10.1002/jcb.23350

Cited by 253 publications

(196 citation statements)

References 48 publications

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“…The IGF-1 signaling may play a less prominent role in MDA-MB-231 cells (44), and other signaling pathways, including Wnt signaling, are important mediators of tumorigenesis in these cells. As klotho is a potent inhibitor of Wnt signaling in other malignancies, it is possible that some of its effects in breast cancer are mediating by affecting Wnt signaling (37,46). Several studies demonstrated a critical role for residues within klotho's putative active site in mediating some of the activities of klotho.…”

Section: Discussionmentioning

confidence: 99%

Tumor Suppressor Activity of Klotho in Breast Cancer Is Revealed by Structure–Function Analysis

Ligumsky

Rubinek

Merenbakh-Lamin

et al. 2015

Molecular Cancer Research

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Klotho is a transmembrane protein containing two internal repeats, KL1 and KL2, both displaying significant homology to members of the b-glycosidase family. Klotho is expressed in the kidney, brain, and various endocrine tissues, but can also be cleaved and act as a circulating hormone. Klotho is an essential cofactor for binding of fibroblast growth factor 23 (FGF23) to the FGF receptor and can also inhibit the insulin-like growth factor-1 (IGF-1) pathway. Data from a wide array of malignancies indicate klotho as a tumor suppressor; however, the structure-function relationships governing its tumor suppressor activities have not been deciphered. Here, the tumor suppressor activities of the KL1 and KL2 domains were examined. Overexpression of either klotho or KL1, but not of KL2, inhibited colony formation by MCF-7 and MDA-MB-231 cells. Moreover, in vivo administration of KL1 was not only well tolerated but significantly slowed tumor formation in nude mice. Further studies indicated that KL1, but not KL2, interacted with the IGF-1R and inhibited the IGF-1 pathway. Based on computerized structural modeling, klotho constructs were generated in which critical amino acids have been mutated. Interestingly, the mutated proteins retained their tumor suppressor activity but showed reduced ability to modulate FGF23 signaling. These data indicate differential activity of the klotho domains, KL1 and KL2, in breast cancer and reveal that the tumor suppressor activities of klotho can be dissected from its physiologic activities.Implications: These findings pave the way for a rational design of safe klotho-based molecules for the treatment of breast cancer.

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Section: Discussionmentioning

confidence: 99%

Tumor Suppressor Activity of Klotho in Breast Cancer Is Revealed by Structure–Function Analysis

Ligumsky

Rubinek

Merenbakh-Lamin

et al. 2015

Molecular Cancer Research

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“…Moreover, the transcriptional knockdown of FZD7 or LRP6 in triple-negative breast cancer cells represses tumor growth (Jamdade et al, 2015). Accumulating evidence demonstrated that activated Wnt/ -catenin signaling participates in the pathological process of breast cancer (King et al, 2012;Lu and Li, 2014;Ma et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

Lycorine inhibits MDA-MB-231 breast cancer cell proliferation, migration and invasion that are associated with Wnt/β-catenin signaling

Chen

2018

Bangladesh J Pharmacol

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Lycorine inhibits MDA-MB-231 breast cancer cell proliferation, migration and invasion that are associated with Wnt/β-catenin signaling BJP IntroductionBreast cancer is the second leading cause of cancer death among women after lung cancer in the United States (DeSantis et al., 2014). In the treatment for breast cancer, some adverse effects could cause serious complications and affect the health and quality of life among survivors (Odle, 2014). Therefore, it is necessary to develop novel anti-cancer candidates for breast cancer.In the past several decades, natural compounds such as resveratrol (Sinha et al., 2016), epigallocatechin-3-gallate, oldenlandia diffusa and Ziziphus jujube have been demonstrated that possessed potential anti-breast cancer activity (Bonofiglio et al., 2016).Lycorine, known as a multifunctional compound, is extensively studied for its pharmacological activities, such as anti-tumor activity (Lamoral-Theys et al., 2010). Previous studies have shown that lycorine presented a potential anti-cancer activity in breast cancer via the inhibition of tumor growth and metastasis Ying et al., 2017). Src/FAK (focal adhesion kinase) -involved pathway and STAT3 (signal transducer and activator of transcription 3) signaling pathway were involved in growth, invasion and metastasis of breast cancer.However, Wnt/ -catenin signaling, a multifunctional pathway that has not been studied to be involved in proliferation, invasion and migration of breast cancer. This study is meant to confirm the inhibitory effects of lycorine on the proliferation, migration and invasion of MDA-MB-231 breast cancer cells and investigate the activation of Wnt/ -catenin signaling pathway involved. Materials and Methods Cell lines and reagentsHuman MDA-MB-231 breast cancer cells were obtained AbstractThis study was aimed to determine the effects of lycorine, a toxic crystalline alkaloid, on MDA-MB-231 breast cancer cells proliferation, migration and invasion, and to investigate the mechanism involved. The cells were cultured with different concentrations of lycorine in vitro. MTT assays were performed to determine the proliferation of cells. Transwell assays were performed to measure the migration and invasion of cells. The activation of Wnt/ -catenin signaling pathway and expression were assayed by Western blot. This study showed that proliferation, migration and invasion of MDA-MB-231 breast cancer cells could be inhibited by lycorine. Furthermore, we found that Wnt/ -catenin signaling was markedly blocked in MDA-MB-321 cells treated with lycorine. In conclusion, lycorine inhibits the proliferation, migration and invasion of MDA-MB-231 breast cancer cells that is associated with the suppression of Wnt/ -catenin signaling. Article Info

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“…Fzd receptors overexpression has a strong correlation with tumor progression and are also expressed in HER2 negative breast cancer cell lines. 46 As Wnt targeting is a new candidate for breast cancer immunotherapy, anti-Fzd7 antibodies could be new alternatives in this regard.…”

Section: Discussionmentioning

confidence: 99%

Developing and characterization of single chain variable fragment (scFv) antibody against frizzled 7 (Fzd7) receptor

et al. 2017

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ABSTACTWnt/b-catenin signaling pathway through Frizzled receptors has been shown to play a key role in both normal development and tumorigenesis. Overexpression of Wnt pathway genes, such as Fzd7 in several malignancies is well-documented. Therefore, targeting of Fzd7 and its ligand inhibits cancer cells proliferation metastasis. In the present study we isolated single chain variable fragments (scFvs) against Fzd7 receptor using phage display method. Semi-synthetic human naive antibody libraries (Tomlinson I C J) was employed in panning procedure to isolate specific scFv against specific peptide from extracellular domain of Fzd7 receptor. The reactivity and growth inhibition effects of the selected antibodies was evaluated using enzyme-linked immunosorbent assay (ELISA), MTT and annexin V assays, respectively. Seven scFvs reactive to Fzd7 were selected following 4 rounds of panning. The results showed that the selected scFvs inhibits cell growth through apoptosis cell death in a triple negative breast cancer cells, MDA-MB-231. Given that Fzd7 and Wnt pathway plays a critical role in tumor progression, selected blocking scFvs represent significant potential for immunotherapy of breast cancer cells.

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The wnt/β‐catenin signaling pathway: A potential therapeutic target in the treatment of triple negative breast cancer

Cited by 253 publications

References 48 publications

Tumor Suppressor Activity of Klotho in Breast Cancer Is Revealed by Structure–Function Analysis

Tumor Suppressor Activity of Klotho in Breast Cancer Is Revealed by Structure–Function Analysis

Lycorine inhibits MDA-MB-231 breast cancer cell proliferation, migration and invasion that are associated with Wnt/β-catenin signaling

Developing and characterization of single chain variable fragment (scFv) antibody against frizzled 7 (Fzd7) receptor

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