IGF-IR signaling in epithelial to mesenchymal transition and targeting IGF-IR therapy: overview and new insights

Li, Heming; Batth, Izhar Singh; Qu, Xiujuan; Xu, Ling; Song, Na; Wang, Ruo–Yu; Liu, Yunpeng

doi:10.1186/s12943-016-0576-5

Cited by 94 publications

(77 citation statements)

References 176 publications

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“…This miRNA negatively regulates the expression of IRS1 (Insulin receptor substrate 1) in the colon cancer cell line HCT116 (107). IRS1 is a key signaling mediator of the insulin/insulin-like growth factor (IGF) system controlling cellular proliferation, differentiation, EMT, and apoptosis in colorectal cancer (140,141). Upon phosphorylation by the insulin receptor, IRS1 binds specifically to cellular proteins containing SH2 domains such as phosphatidylinositol 3-kinase (PI3K) regulatory subunit (p85) or GRB2, leading to activation of PI3K and MAPK signaling pathways, respectively (142,143) (Figure 5).…”

Section: Mir-214mentioning

confidence: 99%

PVT1 Long Non-coding RNA in Gastrointestinal Cancer

2020

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Whole genome and transcriptome sequencing technologies have led to the identification of many long non-coding RNAs (lncRNAs) and stimulated the research of their role in health and disease. LncRNAs participate in the regulation of critical signaling pathways including cell growth, motility, apoptosis, and differentiation; and their expression has been found dysregulated in human tumors. Thus, lncRNAs have emerged as new players in the initiation, maintenance and progression of tumorigenesis. PVT1 (plasmacytoma variant translocation 1) lncRNA is located on chromosomal 8q24.21, a large locus frequently amplified in human cancers and predictive of increased cancer risk in genome-wide association studies (GWAS). Combined, colorectal and gastric adenocarcinomas are the most frequent tumor malignancies and also the leading cause of cancer-related deaths worldwide. PVT1 expression is elevated in gastrointestinal tumors and correlates with poor patient prognosis. In this review, we discuss the mechanisms of action underlying PVT1 oncogenic role in colorectal and gastric cancer such as MYC upregulation, miRNA production, competitive endogenous RNA (ceRNA) function, protein stabilization, and epigenetic regulation. We also illustrate the potential role of PVT1 as prognostic biomarker and its relationship with resistance to current chemotherapeutic treatments.

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Section: Mir-214mentioning

confidence: 99%

PVT1 Long Non-coding RNA in Gastrointestinal Cancer

2020

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“…The synthesis of multifarious signaling molecular events leaded the oncogenesis of BC. Understanding and identifying these signaling mechanisms would enable restrain EMT progress to further therapeutic control cancer metastasis (41)(42)(43).…”

Section: Discussionmentioning

confidence: 99%

SPOCK1 promotes breast cancer progression via interacting with SIX1 and activating AKT/mTOR signaling pathway

Zhang

et al. 2019

Preprint

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SPOCK1 is highly expressed in many types of cancer, which has been recognized as a promoter of cancer progression, while its regulatory mechanism remains to be clear in breast cancer (BC). This study aimed to explore the precise function of SPOCK1 in BC progression and the mechanism by which SPOCK1 was involved in cell proliferation and epithelial-mesenchymal transition (EMT).Immunohistochemistry (IHC) and database analysis displayed that high expression of SPOCK1 was positively associated with histological grade, lymph node metastasis (LN) and poor clinical prognosis in BC. A series of assays both in vitro and in vivo elucidated that altering SPOCK1 level led to distinctly changes in BC cell proliferation and metastasis. Investigations of potential mechanisms revealed that SPOCK1 interacted with SIX1 could enhance cell proliferation, cell cycle and EMT process by activating the AKT/mTOR pathway, whereas inhibition of AKT/mTOR pathway or depletion of SIX1 reversed the effects of SPOCK1 overexpression.Furthermore, SPOCK1 and SIX1 were highly expressed in BC and might indicate poor prognoses. Altogether, SPOCK1/SIX1 promoted BC progression by activating AKT/mTOR pathway to accelerate cell proliferation and metastasis in BC, and SPOCK1/SIX1 might be promising clinical therapeutic targets to prevent BC progression. IMPORTANCE:The incidence of BC is alarmingly high and many patients initially diagnosed without detectable metastases will eventually develop metastatic lesions. The occurrence of metastasis is responsible for the death of many patients, which also represents a big challenge for researchers to improve the survival rates of BC patients.Hence the scientific community pays more attention on cancer targeted therapy. This research is significant for identifying the underlying mechanisms and capabilities of SPOCK1-induced BC activities, which will greatly apply novel targets and new treatment strategies for clinicians, leading to broader biomedical impacts. KEYWORDS: SPOCK1; SIX1; EMT; Breast cancer; AKT/mTOR signaling pathwayBreast cancer (BC), the most frequently diagnosed lethal gynecologic malignancy in women worldwide (1), which is an increasing concern because of its rising incidence. Despite major advances in BC therapy, the prognosis for most patients would be significantly worse once spread metastasized occurs (2). Metastasis is the mainspring for most patient death and represents the fundamental challenge of the clinical treatment for the patients with BC. The initiation and metastasis of BC are intricate processes, which triggered by multiple genes and intracellular signal transduction cross-talks. Thus, looking for valid molecular hallmarks and understanding the mechanisms of BC initiation and metastasis process are urged to put on the agenda. Sparc/osteonectin, cwcv and kazal-like domains proteoglycan 1 (SPOCK1), is also known as TIC1; SPOCK; TESTICAN, belongs to multidomain testicular proteoglycan family (3). This protein family includes SPARC, TESTICAN-2, and TESTICAN-3, which are associated with ...

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“…Epithelial-to-mesenchymal transition (EMT) plays a key role in CRC metastasis [3]. Generally, epithelial cells lose cell polarity and the ability of cell adhesion, penetrate the basement membrane and enter the circulatory system, then initiate and promote the invasion and metastasis of cancer cells [4].…”

Section: Introductionmentioning

confidence: 99%

Tanshinone IIA Inhibits Epithelial-to-mesenchymal Transition Through Regulating β-arrestin1 Mediated β-catenin Signaling Pathway in Colorectal Cancer

Song

Yang

Han

et al. 2020

Preprint

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Background: Tanshinone IIA (Tan IIA) is a major active ingredient extracted from Salvia miltiorrhiza, which has been proved to inhibit metastasis of various cancers including colorectal cancer (CRC). However, the detailed mechanisms of Tan IIA against CRC metastasis are not well explored. Epithelial-to-mesenchymal transition (EMT) exerts an important regulatory role in CRC metastasis, and our previous mechanism studies demonstrated that β-arrestin1 could regulate CRC EMT partly through β-catenin signaling pathway. Therefore, in this work we investigated whether Tan IIA could regulate CRC EMT through β-arrestin1-mediated β-catenin signaling pathway in vivo and in vitro.Methods: The nude mice tail vein metastasis model was established to observe the effect of Tan IIA on CRC lung metastasis in vivo. The lung metastasis was evaluated by living animal imaging and hemaoxylin-eosin staining. The migratory ability of CRC cells in vitro were measured by transwell and wound healing assays. The protein expression and cellular localization of β-arrestin1 and β-catenin were characterized by immunofluorescence staining and western blot. The β-catenin signaling pathway related proteins and EMT associated proteins in CRC cells were detected by western blot and immunohistochemistry. Results: Our results showed that Tan IIA inhibited the lung metastases of CRC cells in vivo and extended the survival time of nude mice. In vitro, Tan IIA increased the expression of E-cadherin, decreased the secretion of Snail, N-cadherin and Vimentin, thus suppressed EMT and the migratory ability of CRC cells. Further study found the mechanism involving in Tan IIA regulating EMT and metastasis, referring to the suppression of β-arrestin1 expression, reduction of β-catenin nuclear localization, thereby the decreased activity of β-catenin signaling. Conclusion: Our data revealed a new mechanism of Tan IIA on the suppression of EMT and metastasis in CRC via β-arrestin1-mediated β-catenin signaling pathway, and provided support for Tan IIA as anti-metastatic agents in CRC.

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IGF-IR signaling in epithelial to mesenchymal transition and targeting IGF-IR therapy: overview and new insights

Cited by 94 publications

References 176 publications

PVT1 Long Non-coding RNA in Gastrointestinal Cancer

PVT1 Long Non-coding RNA in Gastrointestinal Cancer

SPOCK1 promotes breast cancer progression via interacting with SIX1 and activating AKT/mTOR signaling pathway

Tanshinone IIA Inhibits Epithelial-to-mesenchymal Transition Through Regulating β-arrestin1 Mediated β-catenin Signaling Pathway in Colorectal Cancer

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