<scp>DLG</scp>5 suppresses breast cancer stem cell‐like characteristics to restore tamoxifen sensitivity by inhibiting <scp>TAZ</scp> expression

Liu, Jie; Li, Juan; Li, Pingping; Jiang, Yongchao; Chen, He; Wang, Ruiqi; Cao, Fang; Liu, Peijun

doi:10.1111/jcmm.13954

Cited by 27 publications

(20 citation statements)

References 32 publications

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“…The present study revealed that the upregulation of TAZ was induced by aberrant expression of the cYTOR/miR-125a-5p/SRF axis. It was recently reported that DLG5 inhibited TAZ expression to sensitize breast cancer cells to tamoxifen (38). The results further extended the understandings on how TAZ expression was increased during development of tamoxifen resistance in breast cancer cells.…”

Section: Discussionsupporting

confidence: 62%

lncRNA CYTOR promotes tamoxifen resistance in�breast cancer cells via sponging miR‑125a‑5p

Liu

et al. 2019

Int J Mol Med

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development of resistance to endocrine therapy, such as tamoxifen, remains a tricky clinical problem during the treatment of breast cancer. Accumulating evidence suggested that dysregulation of long noncoding (lnc_RNAs contributes to the development of tamoxifen resistance. In the current study, via screening, cytoskeleton regulator RNA (cYTOR) was identified as the most significantly elevated lncRNA in the established tamoxifen resistant McF7 cell lines (McF7/TAM1 and McF7/TAM2) compared with the parental McF7 cells (McF7-P). The ccK-8 assay indicated that silencing of cYTOR increased the sensitivity of McF7/TAM1 and McF7/TAM2 to tamoxifen treatment. Using bioinformatic analysis, it was predicted that microRNA (miR)-125a-5p might bind to cYTOR and the expression of miR-125a-5p was negatively correlated with cYTOR in the tumor tissues of breast cancer. In addition, RT-qPcR and dual luciferase assays validated that cYTOR directly repressed miR-125a-5p expression in breast cancer cells. Through regulation of miR-125a-5p, cYTOR elevated serum response factor (SRF) expression and activated Hippo and mitogen associated protein kinase signaling pathways to promote breast cancer cell survival upon tamoxifen treatment. In the collected tumor tissues of breast cancer in the present study, high expression of cYTOR was detected in tissues from patients with no response to tamoxifen compared with those from patients who were not treated with tamoxifen. A positive correlation between cYTOR and SRF mRNA expression was observed in tissues collected from patients with breast cancer. In conclusion, the results of the present study demonstrated a pivotal role of cYTOR in mediating tamoxifen resistance in breast cancer.

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Section: Discussionsupporting

confidence: 62%

lncRNA CYTOR promotes tamoxifen resistance in�breast cancer cells via sponging miR‑125a‑5p

Liu

et al. 2019

Int J Mol Med

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“…Finally, in response to loss of cell polarity, ECM stiffening, focal adhesions and adherens junctions, a number of activated RTKs and GPCRs signal through Rho GTPases and polymerization of filamentous actin to inhibit LATS activity, eventually leading to YAP nuclear translocation. Loss or reduced expression of components of the cell junction-localized cell polarity protein complexes, including the scaffold proteins Scribble (SCRIB) or CRUMBS or of the members of the discs large homolog family (DLG1 or 5), as is frequently observed in cancer, inhibits MST/LATS/YAP interaction, resulting in YAP nuclear translocation, TEAD and SMAD activation and, eventually, the induction of EMT and cancer cell stemness [126,132,133]. In turn, YAP regulates a number of genes involved in upstream RHO/RAC/ROCK signaling [134,135].…”

Section: Yap/taz In Epithelial-mesenchymal Transition (Emt)mentioning

confidence: 99%

The YAP/TAZ Pathway in Osteogenesis and Bone Sarcoma Pathogenesis

Kovar

Bierbaumer

Radic-Sarikas

2020

Cells

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YAP and TAZ are intracellular messengers communicating multiple interacting extracellular biophysical and biochemical cues to the transcription apparatus in the nucleus and back to the cell/tissue microenvironment interface through the regulation of cytoskeletal and extracellular matrix components. Their activity is negatively and positively controlled by multiple phosphorylation events. Phenotypically, they serve an important role in cellular plasticity and lineage determination during development. As they regulate self-renewal, proliferation, migration, invasion and differentiation of stem cells, perturbed expression of YAP/TAZ signaling components play important roles in tumorigenesis and metastasis. Despite their high structural similarity, YAP and TAZ are functionally not identical and may play distinct cell type and differentiation stage-specific roles mediated by a diversity of downstream effectors and upstream regulatory molecules. However, YAP and TAZ are frequently looked at as functionally redundant and are not sufficiently discriminated in the scientific literature. As the extracellular matrix composition and mechanosignaling are of particular relevance in bone formation during embryogenesis, post-natal bone elongation and bone regeneration, YAP/TAZ are believed to have critical functions in these processes. Depending on the differentiation stage of mesenchymal stem cells during endochondral bone development, YAP and TAZ serve distinct roles, which are also reflected in bone tumors arising from the mesenchymal lineage at different developmental stages. Efforts to clinically translate the wealth of available knowledge of the pathway for cancer diagnostic and therapeutic purposes focus mainly on YAP and TAZ expression and their role as transcriptional co-activators of TEAD transcription factors but rarely consider the expression and activity of pathway modulatory components and other transcriptional partners of YAP and TAZ. As there is a growing body of evidence for YAP and TAZ as potential therapeutic targets in several cancers, we here interrogate the applicability of this concept to bone tumors. To this end, this review aims to summarize our current knowledge of YAP and TAZ in cell plasticity, normal bone development and bone cancer.Cells 2020, 9, 972 2 of 34 co-activators Yes-associated protein 1 (YAP-1, YAP) and its paralogue, the transcriptional co-activator with PDZ-binding motif (TAZ, WWTR1), which are typically controlled on the post-translational level by upstream regulatory signaling pathways in organ development and tissue homeostasis [2,3]. YAP and TAZ were reported to affect self-renewal and lineage commitment of stem cells [4][5][6][7], while hyperactivation of YAP and TAZ have been linked to cancer growth and metastasis in various tumors [8][9][10]. TAZ levels are elevated in approximately 20% of cancers and drive invasion and metastasis [11,12], while YAP is frequently overexpressed or amplified in cancer and was shown to promote resistance to chemotherapy in oncogene-addicted tumors up...

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“…Growing evidence suggests that TAZ promotes resistance to various anti‐cancer therapies including cytotoxic chemotherapy (Moroishi et al , ; Zhan et al , ; Liu et al , ). However, our results showed that TAZ knockdown had no inhibitory effect on the clonogenicity of CR and LR cells (Fig A and ).…”

Section: Discussionmentioning

confidence: 99%

Targeting YAP to overcome acquired resistance to ALK inhibitors in ALK ‐rearranged lung cancer

et al. 2019

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Clinical benefit of ALK tyrosine kinase inhibitors (ALK‐TKIs) in ALK‐rearranged lung cancer has been limited by the inevitable development of acquired resistance, and bypass‐molecular resistance mechanisms remain poorly understood. We investigated a novel therapeutic target through screening FDA‐approved drugs in ALK‐TKI‐resistant models. Cerivastatin, the rate‐limiting enzyme inhibitor of the mevalonate pathway, showed anti‐cancer activity against ALK‐TKI resistance in vitro/in vivo, accompanied by cytoplasmic retention and subsequent inactivation of transcriptional co‐regulator YAP. The marked induction of YAP‐targeted oncogenes (EGFR, AXL, CYR61, and TGFβR2) in resistant cells was abolished by cerivastatin. YAP silencing suppressed tumor growth in resistant cells, patient‐derived xenografts, and EML4‐ALK transgenic mice, whereas YAP overexpression decreased the responsiveness of parental cells to ALK inhibitor. In matched patient samples before/after ALK inhibitor treatment, nuclear accumulation of YAP was mainly detected in post‐treatment samples. High expression of YAP in pretreatment samples was correlated with poor response to ALK‐TKIs. Our findings highlight a crucial role of YAP in ALK‐TKI resistance and provide a rationale for targeting YAP as a potential treatment option for ALK‐rearranged patients with acquired resistance to ALK inhibitors.

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DLG5 suppresses breast cancer stem cell‐like characteristics to restore tamoxifen sensitivity by inhibiting TAZ expression

Cited by 27 publications

References 32 publications

lncRNA CYTOR promotes tamoxifen resistance in�breast cancer cells via sponging miR‑125a‑5p

lncRNA CYTOR promotes tamoxifen resistance in�breast cancer cells via sponging miR‑125a‑5p

The YAP/TAZ Pathway in Osteogenesis and Bone Sarcoma Pathogenesis

Targeting YAP to overcome acquired resistance to ALK inhibitors in ALK ‐rearranged lung cancer

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