TGF-β signaling pathways in cancers

Talar, Beata; Czyż, Małgorzata

doi:10.5604/17322693.1068073

Cited by 11 publications

(11 citation statements)

References 60 publications

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“…Connection of TGF-β to TβRII (type II TGFβ receptor) activates this kinase subunit, increases affinity to TβRI (type I TGFβ receptor) and, consequently, activates TβRI which stimulates phosphorylation of the Smad-3 protein attached to the 3-endosomal SARA protein [38]. The phosphorylated Smad-3 protein forms a heterodimer with Smad-4, and the resulting complex is transported into the nucleus, where—via the MH1 domain—it binds to CAGAC sequences or sequences rich in GC pairs in the promoter regions of many genes [38,39].…”

Section: Effects Of Lead On the Expression Of Cytokines In Brainmentioning

confidence: 99%

“…The phosphorylated Smad-3 protein forms a heterodimer with Smad-4, and the resulting complex is transported into the nucleus, where—via the MH1 domain—it binds to CAGAC sequences or sequences rich in GC pairs in the promoter regions of many genes [38,39]. One of them is the GFAP gene encoding the GFAP astrocyte protein whose production is controlled by factors such as STAT3 and Smad; interestingly, binding to STAT3 or Smad separately does not induce transcription of the GFAP gene; transcription is possible only if the Smad and STAT3 are both associated with the GFAP gene, and a P300 molecule serves as the link between them [40].…”

Section: Effects Of Lead On the Expression Of Cytokines In Brainmentioning

confidence: 99%

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Effect of Lead (Pb) on Inflammatory Processes in the Brain

Chibowska

Baranowska-Bosiacka

Falkowska

et al. 2016

IJMS

120

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That the nervous system is the main target of lead (Pb) has long been considered an established fact until recent evidence has linked the Pb effect on the immune system to the toxic effects of Pb on the nervous system. In this paper, we present recent literature reports on the effect of Pb on the inflammatory processes in the brain, particularly the expression of selected cytokines in the brain (interleukin 6, TGF-β1, interleukin 16, interleukin 18, and interleukin 10); expression and activity of enzymes participating in the inflammatory processes, such as cyclooxygenase 2, caspase 1, nitrogen oxide synthase (NOS 2) and proteases (carboxypeptidases, metalloproteinases and chymotrypsin); and the expression of purine receptors P2X4 and P2X7. A significant role in the development of inflammatory processes in the brain is also played by microglia (residual macrophages in the brain and the spinal cord), which act as the first line of defense in the central nervous system, and astrocytes—Whose most important function is to maintain homeostasis for the proper functioning of neurons. In this paper, we also present evidence that exposure to Pb may result in micro and astrogliosis by triggering TLR4-MyD88-NF-κB signaling cascade and the production of pro-inflammatory cytokines.

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Section: Effects Of Lead On the Expression Of Cytokines In Brainmentioning

confidence: 99%

Section: Effects Of Lead On the Expression Of Cytokines In Brainmentioning

confidence: 99%

Effect of Lead (Pb) on Inflammatory Processes in the Brain

Chibowska

Baranowska-Bosiacka

Falkowska

et al. 2016

IJMS

120

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“…This phenomenon has been observed in many human cancers, most commonly in pancreatic, breast, and colon carcinomas. [17][18][19] The most common mutation is being that of the SMAD-4 protein, which is observed in 50% of patients with pancreatic cancer, 20% with colon cancer, and 10% with lung cancer. [20][21][22][23][24] Similar mutations have been observed in patients with hematological malignancies, including acute myeloid leukemia (AML).…”

Section: Introductionmentioning

confidence: 99%

The distribution and potential prognostic value of SMAD protein expression in chronic lymphocytic leukemia

et al. 2017

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The SMAD proteins are responsible for transducing signals from activated transforming growth factor-beta. This is the first study assessing the expression of SMAD-1/8, SMAD-2/3, SMAD-4, and SMAD-7 in chronic lymphocytic leukemia cells with regard to their clinical significance and potential prognostic value. Overexpression of SMAD-1/8 was observed in 160 chronic lymphocytic leukemia patients compared to 42 healthy volunteers (p = 0.023) and was associated with a more progressive course of the disease (p = 0.016). Moreover, the high expression of SMAD-1/8 correlated with other, well-established prognostic factors, including clinical stage (p = 0.010) and lymphocyte doubling time (p = 0.021). The expression of SMAD-4 was lower in chronic lymphocytic leukemia patients compared with the control group (p = 0.003). Importantly, lower SMAD-4 levels correlated with longer progression-free survival (p = 0.009), progressive course of the disease (p = 0.002), advanced clinical stage (p = 0.0004), elevated beta-2-microglobulin and lactate dehydrogenase levels (p < 0.05), shorter lymphocyte doubling time (p = 0.009), and CD38 antigen expression (p = 0.039). In addition, lower SMAD-4 expression correlated with lower apoptotic index (p = 0.0007) and lower expression of receptors for vascular endothelial growth factors VEGFR-1 and VEGFR-2. A significant association was found between the low expression of inhibitory protein SMAD-7 and both zeta-chain-associated protein kinase 70-negative cells (p = 0.04) and lower apoptotic index (p = 0.004). No differences were observed in SMAD-2/3 expression. In conclusion, our results demonstrate a significant correlation between greater SMAD-1/8 and lower SMAD-4 expression in chronic lymphocytic leukemia cells, as well as more progressive outcome and poor prognosis. These data provide supporting evidence that the expression of SMAD proteins plays an important role in disease development and may be considered as a novel, biologic prognostic factor in this disease.

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“…Moreover, TGF-β plays a critical role in the pathogenesis of several diseases along with cancer. Depending on the pathological processes, TGF-β-induced signaling pathways have either tumor-suppressor or tumor-promoting effects [50]. Through the canonical (Smad-dependent) and noncanonical pathways, TGF-β interacts with a wide variety of ECM molecules such as fibronectin, proteoglycans, integrins, CTGF, plasminogen activator inhibitor-1 (PAI-1), MMPs, etc.…”

Section: Cellular Component Of Connective Tissuementioning

confidence: 99%

Extracellular matrix in obesity – cancer interactions

Barreto¹,

Hopkins²,

Bhowmick³

et al. 2015

Hormone Molecular Biology and Clinical Investigation

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Obesity or overweight is a risk factor for several health disorders such as type 2 diabetes, hypertension, and certain cancers. Furthermore, obesity affects almost all body systems including the extracellular matrix (ECM) by generating a pro-inflammatory environment, which are associated with abnormal secretions of several cytokines or hormonal substances, for example, insulin-like growth factors (IGFs), leptin, and sex hormones. These chemical mediators most likely have a great impact on the ECM. Accumulating evidence suggests that both obesity and ECM can influence tumor growth and progression through a number of chemical mediators. Conversely, cells in the connective tissue, namely fibroblasts and macrophages, support and aggravate the inflammatory situation in obesity by releasing several cytokines or growth factors such as vascular endothelial growth factor, epidermal growth factor, and transforming growth factor-beta (TGF-β). A wide range of functions are performed by TGF-β in normal health and pathological conditions including tumorigenesis. Breast cancer in postmenopausal women is a classic example of obesity-related cancer wherein several of these conditions, for example, higher levels of pro-inflammatory cytokines, impairment in the regulation of estrogen and growth factors, and dysregulation of different ECM components may favor the neoplastic process. Aberrant expressions of ECM components such as matrix metalloproteinases or matricellular proteins in both obesity and cancer have been reported by many studies. Nonstructural matricellular proteins, viz., thrombospondins, secreted protein acidic and rich in cysteine (SPARC), and Cyr61-CTGF-Nov (CCN), which function as modulators of cell-ECM interactions, exhibit protean behavior in cancer. Precise understanding of ECM biology can provide potential therapeutic targets to combat obesity-related pathologies.

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TGF-β signaling pathways in cancers

Cited by 11 publications

References 60 publications

Effect of Lead (Pb) on Inflammatory Processes in the Brain

Effect of Lead (Pb) on Inflammatory Processes in the Brain

The distribution and potential prognostic value of SMAD protein expression in chronic lymphocytic leukemia

Extracellular matrix in obesity – cancer interactions

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