TGF-β1 acts through miR-155 to down-regulate TP53INP1 in promoting epithelial–mesenchymal transition and cancer stem cell phenotypes

Liu, Fengchao; Kong, Xin; Lv, Lin; Gao, Jian

doi:10.1016/j.canlet.2015.01.030

Cited by 89 publications

(72 citation statements)

References 52 publications

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“…In addition, it was shown that miR-155 expression was up-regulated in non-parenchymal liver cells during HCV infection and that IL-10, TGF-β and miR-155 may regulate the TLR3-dependent antiviral and inflammatory activity of non-parenchymal liver cells in vitro [155]. Besides, miR-155 overexpression not only strongly enhanced the EMT process and cell invasion but also increased the population of stem-like CSCs among liver cancer cells [156]. Furthermore, knockdown of miR-155 in Kupffer cells resulted in immunosuppressive effects and prolonged mice survival using a liver allografts model [157].…”

Section: Inflammation-related Signaling Pathwaysmentioning

confidence: 99%

Involvement of inflammation and its related microRNAs in hepatocellular carcinoma

Jin

Sánchez‐Duffhues

et al. 2016

Oncotarget

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Hepatocellular carcinoma (HCC) is the fifth most commonly diagnosed type of cancer. The tumor inflammatory microenvironment regulates almost every step towards liver tumorigenesis and subsequent progression, and regulation of the inflammation-related signaling pathways, cytokines, chemokines and non-coding RNAs influences the proliferation, migration and metastasis of liver tumor cells. Inflammation fine-tunes the cancer microenvironment to favor epithelial-mesenchymal transition, in which cancer stem cells maintain tumorigenic potential. Emerging evidence points to inflammation-related microRNAs as crucial molecules to integrate the complex cellular and molecular crosstalk during HCC progression. Thus understanding the mechanisms by which inflammation regulates microRNAs might provide novel and admissible strategies for preventing, diagnosing and treating HCC. In this review, we will update three hypotheses of hepatocarcinogenesis and elaborate the most predominant inflammation signaling pathways, i.e. IL-6/STAT3 and NF-κB. We also try to summarize the crucial tumor-promoting and tumor-suppressing microRNAs and detail how they regulate HCC initiation and progression and collaborate with other critical modulators in this review.

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Section: Inflammation-related Signaling Pathwaysmentioning

confidence: 99%

Involvement of inflammation and its related microRNAs in hepatocellular carcinoma

Jin

Sánchez‐Duffhues

et al. 2016

Oncotarget

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“…(35) The EMT has been reported to play an essential role in regulating CSCs, which often exhibit an EMT phenotype in HCC. (36) In our study, we observed that a chronic hypoxic microenvironment due to insufficient RFA generated more CD90 + cells without impacting CD133 expression and that down-regulation of HIF-1a reduced the percentage of CD90 + cells. This suggested that the HIF-1a pathway is involved in CSC regulation.…”

Section: Discussionmentioning

confidence: 57%

Effect of a Hypoxic Microenvironment after Radiofrequency Ablation on Residual Hepatocellular Cell Migration and Invasion

Tong

Luo

2017

Ultrasound in Medicine & Biology

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Clinical observations have shown that the boundary of tumor ablation is often less than safe border and that the use of radiofrequency ablation (RFA) in the treatment of hepatocellular carcinoma (HCC) may probably accelerate its recurrence and metastasis. RFA can cause the formation of a transition zone between normal liver tissues and necrotic coagulation, where blood stagnation and thrombosis expose residual cancer cells to a hypoxic microenvironment. As the blocked vessels are slowly reperfused, the oxygen supply is gradually restored. Here, HCC cells underwent heat treatment and were cultured under hypoxic conditions to mimic the aforementioned situation, and morphological changes were observed in the surviving cells. Compared with their parental cells, hypoxic HCC cells showed changes that include enhanced invasive, metastatic, and chemoresistant abilities as well as mesenchymal characteristics. There was also a higher percentage of stem-like cells. However, either improving the hypoxic microenvironment or silencing hypoxia inducible factor (HIF)-1a signaling significantly reduced the invasive, metastatic, and chemoresistant potential and reversed the epithelialmesenchymal transition to varying degrees. Together, these results indicated that a sustained hypoxic microenvironment after RFA may exert a negative impact on the prognosis of HCC patients, and minimizing exposure to a hypoxic microenvironment and targeting HIF-1a signaling might be effective strategies for patients who experience insufficient RFA therapy.H epatocellular carcinoma (HCC) ranks as the third most frequent cause of cancer-related death.(1) Although surgical operation and transplantation have been recognized as the primary curative therapies for patients with HCC, the advanced neoplastic stage, severe liver dysfunction and shortage of available liver grafts restrict their application.(2) Radiofrequency ablation (RFA) therapy has emerged as an alternative due to its minimal invasiveness, safety, and shorter hospital stays. The survival of patients with HCC <3 cm treated by RFA competes with that of surgical candidates.(3) However, suboptimal RFA treatment of HCC has been reported as a risk factor of early diffuse recurrence, (4) and large tumor size is an independent risk factor of local recurrence because of its poorly defined margins.(5) The necrotic lesion generated by RFA is surrounded by a rim of chronically hypoxic liver tissue, where aggressive outgrowth of residual hepatic micro-metastases has been observed.(6) A hypoxic microenvironment contributes to the development of a malignant phenotype, which includes local invasion, metastatic progression, and chemoresistance. Hypoxia inducible factor (HIF)-1a is a key mediator of cellular adaption to hypoxia (8) and can facilitate the progression of various cancer cells by promoting cell migration, tumor angiogenesis, and metastasis.(9) The epithelial-mesenchymal transition (EMT) has long been recognized as an important step in the progression of primary tumors to distant metastasis.(10) ...

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“…The activation of TGF-β1 signaling triggers the epithelial-mesenchymal transition (EMT) and ensures that the transformed cancer cells possess a stronger capacity of self-renewal, tumorigenesis, and chemo-/radioresistance [52]. In OS or other tumor types, solid evidence suggests that TGF-β1 is responsible for promoting stemness [5,53]. The TGF-β1 inhibitor SB525334 signiicantly inhibited the migration and invasion of sphere-forming stemlike cells [54].…”

Section: Tgf-β1mentioning

confidence: 99%

Microenvironment Signals and Mechanisms in the Regulation of Osteosarcoma

Mai¹,

Zhang²,

Xie³

et al. 2017

Osteosarcoma - Biology, Behavior and Mechanisms

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Osteosarcoma (OS) is the most common malignant primary bone tumor in children and adolescents and features rapid development, strong metastatic ability, and poor prognosis. It has been well established that diverse genetic aberrations and metabolic alterations confer the tumorigenesis and development of OS. The intricate metabolism and vascularization that contributes to the nutrient and structural support for tumor progression should be thoroughly clariied to help us gain novel insights into OS and its clinical diagnoses and treatments. With regard to the complex bone extracellular matrix (ECM) and local cell populations, we intend to illustrate the interrelationship between various microenvironmental signals and the diferent stages of OS evolution. Solid evidence has noted two crucial factors of the OS microenvironment in the acquisition of stem cell phenotypes -transforming growth factor-β1 (TGF-β1) signaling and hypoxia. Diferent cell subtypes in the local environment might also serve as unique contributors that interact with each other and communicate with distant cells, thus participating in local invasion and metastasis. Proper models have been established and improved to reveal the evolutionary footsteps of how normal cells transform into a neoplastic state and progress toward malignancy.

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TGF-β1 acts through miR-155 to down-regulate TP53INP1 in promoting epithelial–mesenchymal transition and cancer stem cell phenotypes

Cited by 89 publications

References 52 publications

Involvement of inflammation and its related microRNAs in hepatocellular carcinoma

Involvement of inflammation and its related microRNAs in hepatocellular carcinoma

Effect of a Hypoxic Microenvironment after Radiofrequency Ablation on Residual Hepatocellular Cell Migration and Invasion

Microenvironment Signals and Mechanisms in the Regulation of Osteosarcoma

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