scholarly journals Role of Endoglin (CD105) in the Progression of Hepatocellular Carcinoma and Anti-Angiogenic Therapy

2018 ◽  
Vol 19 (12) ◽  
pp. 3887 ◽  
Author(s):  
Aldona Kasprzak ◽  
Agnieszka Adamek
Keyword(s):  
Hepatocellular Carcinoma ◽  
Molecular Mechanisms ◽  
Transforming Growth Factor ◽  
Primary Liver Cancer ◽  
Venous Blood ◽  
Transforming Growth Factor Β ◽  
Current Data ◽  
Solid Tumours ◽  
Angiogenic Therapy

The liver is perfused by both arterial and venous blood, with a resulting abnormal microenvironment selecting for more-aggressive malignancies. Hepatocellular carcinoma (HCC) is the most frequent primary liver cancer, the sixth most common cancer globally, and the third leading cause of cancer-related mortality worldwide. HCC is characterized by its hypervascularization. Improving the efficiency of anti-angiogenic treatment and mitigation of anti-angiogenic drug resistance are the top priorities in the development of non-surgical HCC therapies. Endoglin (CD105), a transmembrane glycoprotein, is one of the transforming growth factor β (TGF-β) co-receptors. Involvement of that protein in angiogenesis of solid tumours is well documented. Endoglin is a marker of activated endothelial cells (ECs), and is preferentially expressed in the angiogenic endothelium of solid tumours, including HCC. HCC is associated with changes in CD105-positive ECs within and around the tumour. The large spectrum of endoglin effects in the liver is cell-type- and HCC- stage-specific. High expression of endoglin in non-tumour tissue suggests that this microenvironment might play an especially important role in the progression of HCC. Evaluation of tissue expression, as well as serum concentrations of this glycoprotein in HCC, tends to confirm its role as an important biomarker in HCC diagnosis and prognosis. The role of endoglin in liver fibrosis and HCC progression also makes it an attractive therapeutic target. Despite these facts, the exact molecular mechanisms of endoglin functioning in hepatocarcinogenesis are still poorly understood. This review summarizes the current data concerning the role and signalling pathways of endoglin in hepatocellular carcinoma development and progression, and provides an overview of the strategies available for a specific targeting of CD105 in anti-angiogenic therapy in HCC.

scholarly journals The Potential Association between the Risk of Post-Surgical Adhesion and the Activated Local Angiotensin II Type 1 Receptors: Need for Novel Treatment Strategies

2021 ◽  
pp. 1-8
Author(s):  
Mahmood Tavakkoli ◽  
Saeed Aali ◽  
Borzoo Khaledifar ◽  
Gordon A. Ferns ◽  
Majid Khazaei ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Molecular Mechanisms ◽  
Transforming Growth Factor ◽  
Therapeutic Potential ◽  
Angiotensin Receptor Blockers ◽  
Surgical Techniques ◽  
Treatment Strategies ◽  
Transforming Growth Factor Β

<b><i>Background:</i></b> Post-surgical adhesion bands (PSABs) are a common complication after abdominal or pelvic surgeries for different reasons like cancer treatment. Despite improvements in surgical techniques and the administration of drugs or the use of physical barriers, there has only been limited improvement in the frequency of postoperative adhesions. Complications of PSAB are pain, infertility, intestinal obstruction, and increased mortality. The most important molecular mechanisms for the development of PSAB are inflammatory response, oxidative stress, and overexpression of pro-fibrotic molecules such as transforming growth factor β. However, questions remain about the pathogenesis of this problem, for example, the causes for individual differences or why certain tissue sites are more prone to post-surgical adhesions. <b><i>Summary:</i></b> Addressing the pathological causes of PSAB, the potential role of local angiotensin II/angiotensin II type 1 receptors (AngII/AT1R), may help to prevent this problem. <b><i>Key Message:</i></b> The objective of this article was to explore the role of the AngII/AT1R axis potential to induce PSAB and the therapeutic potential of angiotensin receptor blockers in the prevention and treatment of PSAB.

scholarly journals The Role of Endoglin in Hepatocellular Carcinoma

2021 ◽  
Vol 22 (6) ◽  
pp. 3208
Author(s):  
Kuo-Shyang Jeng ◽  
I-Shyan Sheen ◽  
Shu-Sheng Lin ◽  
Chuen-Miin Leu ◽  
Chiung-Fang Chang
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Diseases ◽  
Transforming Growth Factor ◽  
Antiangiogenic Therapy ◽  
Transforming Growth Factor Β ◽  
Postoperative Recurrence ◽  
Transmembrane Glycoprotein ◽  
Early Progression

Endoglin (CD105) is a type-1 integral transmembrane glycoprotein and coreceptor for transforming growth factor-β (TGF-β) ligands. The endoglin/TGF-β signaling pathway regulates hemostasis, cell proliferation/migration, extracellular matrix (ECM) synthesis and angiogenesis. Angiogenesis contributes to early progression, invasion, postoperative recurrence, and metastasis in hepatocellular carcinoma (HCC), one of the most widespread malignancies globally. Endoglin is overexpressed in newly formed HCC microvessels. It increases microvessel density in cirrhotic and regenerative HCC nodules. In addition, circulating endoglin is present in HCC patients, suggesting potential for use as a diagnostic or prognostic factor. HCC angiogenesis is dynamic and endoglin expression varies by stage. TRC105 (carotuximab) is an antibody against endoglin, and three of its clinical trials were related to liver diseases. A partial response was achieved when combining TRC105 with sorafenib. Although antiangiogenic therapy still carries some risks, combination therapy with endoglin inhibitors or other targeted therapies holds promise.

pVHL-mediated SMAD3 degradation suppresses TGF-β signaling

2021 ◽  
Vol 221 (1) ◽  
Author(s):  
Jun Zhou ◽  
Yasamin Dabiri ◽  
Rodrigo A. Gama-Brambila ◽  
Shahrouz Ghafoory ◽  
Mukaddes Altinbay ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Tissue Homeostasis ◽  
Wing Development ◽  
Dynamic Regulation ◽  
Drosophila Wing ◽  
Wing Growth ◽  
Expression And Activity

Transforming growth factor β (TGF-β) signaling plays a fundamental role in metazoan development and tissue homeostasis. However, the molecular mechanisms concerning the ubiquitin-related dynamic regulation of TGF-β signaling are not thoroughly understood. Using a combination of proteomics and an siRNA screen, we identify pVHL as an E3 ligase for SMAD3 ubiquitination. We show that pVHL directly interacts with conserved lysine and proline residues in the MH2 domain of SMAD3, triggering degradation. As a result, the level of pVHL expression negatively correlates with the expression and activity of SMAD3 in cells, Drosophila wing, and patient tissues. In Drosophila, loss of pVHL leads to the up-regulation of TGF-β targets visible in a downward wing blade phenotype, which is rescued by inhibition of SMAD activity. Drosophila pVHL expression exhibited ectopic veinlets and reduced wing growth in a similar manner as upon loss of TGF-β/SMAD signaling. Thus, our study demonstrates a conserved role of pVHL in the regulation of TGF-β/SMAD3 signaling in human cells and Drosophila wing development.

scholarly journals Role of the Transforming Growth Factor-β in regulating hepatocellular carcinoma oxidative metabolism

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Jitka Soukupova ◽  
Andrea Malfettone ◽  
Petra Hyroššová ◽  
María-Isabel Hernández-Alvarez ◽  
Irene Peñuelas-Haro ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Growth Factor ◽  
Oxidative Metabolism ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β

scholarly journals The Dual Role of STAT1 in Ovarian Cancer: Insight Into Molecular Mechanisms and Application Potentials

2021 ◽  
Vol 9 ◽  
Author(s):  
Xin Li ◽  
Fanchen Wang ◽  
Xiaolin Xu ◽  
Jinguo Zhang ◽  
Guoxiong Xu
Keyword(s):  
Ovarian Cancer ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Transforming Growth Factor ◽  
Early Stage ◽  
Transforming Growth Factor Β ◽  
Janus Kinase ◽  
Atypical Symptoms ◽  
Stat1 Signaling

The signal transducer and activator of transcription 1 (STAT1) is a transducer protein and acts as a transcription factor but its role in ovarian cancer (OC) is not completely understood. Practically, there are two-faced effects of STAT1 on tumorigenesis in different kinds of cancers. Existing evidence reveals that STAT1 has both tumor-suppressing and tumor-promoting functions involved in angiogenesis, cell proliferation, migration, invasion, apoptosis, drug resistance, stemness, and immune responses mainly through interacting and regulating target genes at multiple levels. The canonical STAT1 signaling pathway shows that STAT1 is phosphorylated and activated by the receptor-activated kinases such as Janus kinase in response to interferon stimulation. The STAT1 signaling can also be crosstalk with other signaling such as transforming growth factor-β signaling involved in cancer cell behavior. OC is often diagnosed at an advanced stage due to symptomless or atypical symptoms and the lack of effective detection at an early stage. Furthermore, patients with OC often develop chemoresistance and recurrence. This review focuses on the multi-faced role of STAT1 and highlights the molecular mechanisms and biological functions of STAT1 in OC.

scholarly journals Activation of the transforming growth factor-β/SMAD transcriptional pathway underlies a novel tumor-promoting role of sulfatase 1 in hepatocellular carcinoma

Hepatology ◽  
2015 ◽  
Vol 61 (4) ◽  
pp. 1269-1283 ◽  
Author(s):  
Renumathy Dhanasekaran ◽  
Ikuo Nakamura ◽  
Chunling Hu ◽  
Gang Chen ◽  
Abdul M. Oseini ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Transcriptional Pathway

scholarly journals Knockdown of Latent Transforming Growth Factor-β (TGF-β)-Binding Protein 2 (LTBP2) Inhibits Invasion and Tumorigenesis in Thyroid Carcinoma Cells

2017 ◽  
Vol 25 (4) ◽  
pp. 503-510 ◽  
Author(s):  
Fuqiang Wan ◽  
Li Peng ◽  
ChaoYu Zhu ◽  
XinFa Zhang ◽  
FangWen Chen ◽  
...  
Keyword(s):  
Growth Factor ◽  
Thyroid Carcinoma ◽  
Molecular Mechanisms ◽  
Transforming Growth Factor ◽  
Binding Protein ◽  
Transforming Growth Factor Β ◽  
Vital Role ◽  
Carcinoma Cells ◽  
Human Thyroid

Latent transforming growth factor-β (TGF-β)-binding protein 2 (LTBP2) is one of four proteins in the LTBP family of proteins (LTBP1‐4) and was shown to play a vital role in tumorigenesis. However, little is known regarding the functional role of LTBP2 in thyroid carcinoma. Therefore, the current study aimed to evaluate the effect of LTBP2 expression on the proliferation, invasion, and tumorigenesis in thyroid carcinoma cells and to explore the molecular mechanism of LTBP2 in tumor progression. Our results showed that the expression of LTBP2 is upregulated in human thyroid carcinoma and cell lines. Knockdown of LTBP2 inhibits the proliferation, invasion, and EMT phenotype in thyroid carcinoma cells. Furthermore, knockdown of LTBP2 attenuates thyroid carcinoma growth in nude mice. Finally, knockdown of LTBP2 inhibits activation of the PI3K/Akt pathway in thyroid carcinoma cells. In summary, the present study has provided further evidence that knockdown of LTBP2 inhibits invasion and tumorigenesis in thyroid carcinoma cells. Our findings may help to further elucidate the molecular mechanisms underlying thyroid carcinoma progression and provide candidate targets for the prevention and treatment of thyroid carcinoma.

scholarly journals Molecular mechanisms of circular RNAs, transforming growth factor‐ β , and long noncoding RNAs in hepatocellular carcinoma

2019 ◽  
Vol 8 (15) ◽  
pp. 6684-6699 ◽  
Author(s):  
Wenkang Shang ◽  
Gabriel Komla Adzika ◽  
Yujie Li ◽  
Qike Huang ◽  
Ningding Ding ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Growth Factor ◽  
Molecular Mechanisms ◽  
Transforming Growth Factor ◽  
Noncoding Rnas ◽  
Transforming Growth Factor Β ◽  
Long Noncoding Rnas ◽  
Circular Rnas

scholarly journals Possible role of transforming growth factor β as a marker cytokine of type 3 T-helpers in atopic dermatitis pathogenesis

2004 ◽  
Vol 3 (3) ◽  
pp. 27-31
Author(s):  
N. A. Pronina ◽  
V. S. Sviridova ◽  
A. A. Denisov ◽  
V. V. Klimov ◽  
Ye. N. Kologrivova
Keyword(s):  
Atopic Dermatitis ◽  
Biological Activity ◽  
Growth Factor ◽  
Molecular Mechanisms ◽  
Transforming Growth Factor ◽  
Allergic Inflammation ◽  
Transforming Growth Factor Β ◽  
Cell Populations ◽  
Type 3

The role of transforming growth factor β (TGF-β) in atopic dermatitis pathogenesis is discussed basing on the analysis of existing data of cellular and molecular mechanisms of allergic inflammation. Up-to date data of the main T-helper (T-h) lymphocyte subpopulations including Tx1, Tx2, Tx3 has been presented. Functions of regulatory T-cell populations and produced cytokines have been described. The main attention has been accented on the TGF-β structure and biological activity as a main Tx3 cytokine. The current information of TGF-β influence on different cell populations and its biological activity realization mechanism is thoroughly discussed. Information relating to the mechanism of cytokine regulation during atopic dermatitis has been summarized. A deep analysis of possible participation of TGF-β in disbalance formation on Tx1 and Tx2 levels, in disturbances of histological derma structure and allergic inflammation timing has been made.

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