TIAM1 Antagonizes TAZ/YAP Both in the Destruction Complex in the Cytoplasm and in the Nucleus to Inhibit Invasion of Intestinal Epithelial Cells

Diamantopoulou, Zoi; White, Gavin R M; Fadlullah, Muhammad Zaki Hidayatullah; Dreger, Marcel; Pickering, Karen; Maltas, Joe; Ashton, Garry; MacLeod, Ruth; Baillie, George S.; Kouskoff, Valérie; Lacaud, Georges; Murray, Graeme I.; Sansom, Owen J.; Hurlstone, Adam; Malliri, Angeliki

doi:10.1016/j.ccell.2017.03.007

Cited by 78 publications

(72 citation statements)

References 55 publications

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“…Cell proliferation is a vital process for normal development of our body and brain. For a long time, YAP is known to be an important regulator of cell proliferation, regardless of normal cell or tumour cells . Moreover, YAP can prevent reactive astrogliosis .…”

Section: Discussionmentioning

confidence: 99%

YAP promotes the proliferation of neuroblastoma cells through decreasing the nuclear location of p27^Kip1 mediated by Akt

Shen

Xie

et al. 2019

Cell Proliferation

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Objective We aimed to investigate the roles and underlying mechanisms of YAP in the proliferation of neuroblastoma cells. Methods The expression level of YAP was evaluated by Western blotting and immunocytochemistry. Cell viability, cell proliferation and growth were detected by CCK‐8, PH3 and Ki67 immunostaining, and the real‐time cell analyser system. The nuclear and cytoplasmic proteins of p27Kip1 were dissociated by the nuclear‐cytosol extraction kit and were detected by Western blotting and immunocytochemistry. mRNA levels of Akt, CDK5 and CRM1 were determined by qRT‐PCR. Results YAP was enriched in SH‐SY5Y cells (a human neuroblastoma cell line). Knock‐down of YAP in SH‐SY5Y cells or SK‐N‐SH cell line (another human neuroblastoma cell line) significantly decreased cell viability, inhibited cell proliferation and growth. Mechanistically, knock‐down of YAP increased the nuclear location of p27Kip1, whereas serum‐induced YAP activation decreased the nuclear location of p27Kip1 and was required for cell proliferation. Meanwhile, overexpression of YAP in these serum‐starved SH‐SY5Y cells decreased the nuclear location of p27Kip1, promoted cell proliferation and overexpression of p27Kip1 in YAP‐activated cells inhibited cell proliferation. Furthermore, knock‐down of YAP reduced Akt mRNA and protein levels. Overexpression of Akt in YAP‐downregulated cells decreased the nuclear location of p27Kip1 and accelerated the proliferation of SH‐SY5Y cells. Conclusions Our studies suggest that YAP promotes the proliferation of neuroblastoma cells through negatively controlling the nuclear location of p27Kip1 mediated by Akt.

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Section: Discussionmentioning

confidence: 99%

YAP promotes the proliferation of neuroblastoma cells through decreasing the nuclear location of p27^Kip1 mediated by Akt

Shen

Xie

et al. 2019

Cell Proliferation

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“…[173][174][175] In the cytoplasm, TAZ/YAP interacts directly with β-catenin and restricts β-catenin degradation, 176 but TIAM1 antagonizes TAZ/YAP accumulation and translocation from the cytoplasm to the nucleus. 177 Moreover, CDH11 inhibits the migration and invasion of colorectal CSCs by inhibiting Wnt/ β-catenin and AKT/RhoA signaling. 165 Wnt signaling decreases the expression of HOXA5 to promote CSC metastasis.…”

Section: Major Signaling Pathways In Cscsmentioning

confidence: 99%

Targeting cancer stem cell pathways for cancer therapy

Yang

Shi

Zhao

et al. 2020

Sig Transduct Target Ther

1,318

998

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Since cancer stem cells (CSCs) were first identified in leukemia in 1994, they have been considered promising therapeutic targets for cancer therapy. These cells have self-renewal capacity and differentiation potential and contribute to multiple tumor malignancies, such as recurrence, metastasis, heterogeneity, multidrug resistance, and radiation resistance. The biological activities of CSCs are regulated by several pluripotent transcription factors, such as OCT4, Sox2, Nanog, KLF4, and MYC. In addition, many intracellular signaling pathways, such as Wnt, NF-κB (nuclear factor-κB), Notch, Hedgehog, JAK-STAT (Janus kinase/signal transducers and activators of transcription), PI3K/AKT/mTOR (phosphoinositide 3-kinase/AKT/mammalian target of rapamycin), TGF (transforming growth factor)/SMAD, and PPAR (peroxisome proliferator-activated receptor), as well as extracellular factors, such as vascular niches, hypoxia, tumor-associated macrophages, cancer-associated fibroblasts, cancer-associated mesenchymal stem cells, extracellular matrix, and exosomes, have been shown to be very important regulators of CSCs. Molecules, vaccines, antibodies, and CAR-T (chimeric antigen receptor T cell) cells have been developed to specifically target CSCs, and some of these factors are already undergoing clinical trials. This review summarizes the characterization and identification of CSCs, depicts major factors and pathways that regulate CSC development, and discusses potential targeted therapy for CSCs.Signal Transduction and Targeted Therapy (2020) 5:8; https://doi.

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“…rRNA and protein biosynthesis are key requirements for abnormal cancer cell proliferation, and rRNA biogenesis inhibitors are currently in clinical trials as anti-cancer agents (30,42). The recent intriguing finding that nuclear Tiam1 is a negative regulator of colorectal cancer cell proliferation and invasion via suppression of a TAZ/YAP genetic program, and that it serves as a good prognostic factor for colorectal cancer patients (44) highlights the complexities of Rac-GEF signaling in different cancer types. Overall, these new findings indicate that different subcellular pools of Rac controlled by specific Rac-GEFs play distinctive roles in cancer progression.…”

Section: Emerging Paradigms In Rho Gtpase Hyperactivation In Cancermentioning

confidence: 99%

The Rac GTPase in Cancer: From Old Concepts to New Paradigms

2017

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Rho family GTPases are critical regulators of cellular functions that play important roles in cancer progression. Aberrant activity of Rho small G-proteins, particularly Rac1 and their regulators, is a hallmark of cancer, and contributes to the tumorigenic and metastatic phenotypes of cancer cells. This review examines the multiple mechanisms leading to Rac1 hyperactivation, particularly focusing on emerging paradigms that involve gain-of-function mutations in Rac and guanine nucleotide exchange factors (GEFs), defects in Rac1 degradation, and mislocalization of Rac signaling components. The unexpected pro-oncogenic functions of Rac GTPase activating proteins (GAPs) also challenged the dogma that these negative Rac regulators solely act as tumor suppressors. The potential contribution of Rac hyperactivation to resistance to anti-cancer agents, including targeted therapies, as well as to the suppression of anti-tumor immune response, highlights the critical need to develop therapeutic strategies to target the Rac pathway in a clinical setting.

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TIAM1 Antagonizes TAZ/YAP Both in the Destruction Complex in the Cytoplasm and in the Nucleus to Inhibit Invasion of Intestinal Epithelial Cells

Cited by 78 publications

References 55 publications

YAP promotes the proliferation of neuroblastoma cells through decreasing the nuclear location of p27^Kip1 mediated by Akt

YAP promotes the proliferation of neuroblastoma cells through decreasing the nuclear location of p27^Kip1 mediated by Akt

Targeting cancer stem cell pathways for cancer therapy

The Rac GTPase in Cancer: From Old Concepts to New Paradigms

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TIAM1 Antagonizes TAZ/YAP Both in the Destruction Complex in the Cytoplasm and in the Nucleus to Inhibit Invasion of Intestinal Epithelial Cells

Cited by 78 publications

References 55 publications

YAP promotes the proliferation of neuroblastoma cells through decreasing the nuclear location of p27Kip1 mediated by Akt

YAP promotes the proliferation of neuroblastoma cells through decreasing the nuclear location of p27Kip1 mediated by Akt

Targeting cancer stem cell pathways for cancer therapy

The Rac GTPase in Cancer: From Old Concepts to New Paradigms

Contact Info

Product

Resources

About

YAP promotes the proliferation of neuroblastoma cells through decreasing the nuclear location of p27^Kip1 mediated by Akt

YAP promotes the proliferation of neuroblastoma cells through decreasing the nuclear location of p27^Kip1 mediated by Akt