This reinforces the role of CTGF protein as a key regulator of MM malignancy. Additionally, PDGFR activation led to the phosphorylation of mTOR and 4E-BP1, critical regulators of protein synthesis downstream of AKT, suggesting that PDGFR controls CTGF protein expression through the regulation of CTGF mRNA translation.

DCP exhibits a protective effect against radiation-induced fibrosis.

P3, N=284, Completed, FibroGen | Active, not recruiting --> Completed

A mutual interplay emerged, where PI3K-Akt signaling could upregulate certain genes, forming feedback loops and intensifying cancer phenotypes. The interconnected overexpression of genes and the PI3K-Akt pathway fosters gastric tumorigenesis, suggesting therapeutic potential. DrugBank analysis identified limited FDA-approved drugs, advocating for further exploration while targeting these hub genes could reshape GC treatment. The identified genes could be novel diagnostic/prognostic biomarkers or potential therapeutic targets for GC, but further clinical validation is required.

Furthermore, overexpression of IGF2BP1 or CTGF reversed the inhibitory effect of LINC00513 shRNA on CRC progression. LINC00513 promoted CRC cell malignant behaviors through IGF2BP1/CTGF.

SWE and CTGF are of great value in the risk assessment of PTC. The degree of fibrosis of PTC is closely related to the prognosis. The hardness of PTC lesions and the expression level of CTGF are correlated with the main indexes of conventional ultrasound differentiating benign or malignant nodules. Irregular shape, aspect ratio ≥ 1, and increased TSH are independent factors of CTGF.

Circ_0000099 can regulate CTGF expression by targeting miR-223-3p. Circ_0000099 silencing might relieve TGF-2-induced SRA01/04 cell injury by the miR-223-3p/CTGF axis, providing new avenues for the prevention and treatment of PCO.

Pharmacological targeting of the Hippo pathway inhibits in-vitro vasculogenic mimicry. Unraveling the connections between the Hippo pathway and vasculogenic mimicry may pave the way for innovative therapeutic strategies.

Pretreatment with MPT0E028 reduced the fibrosis score and fibronectin, collagen, and α-SMA expression in bleomycin-induced pulmonary fibrosis mice. In conclusion, MPT0E028 induced MKP-1 acetylation and activation, which in turn inhibited TGF-β-stimulated JNK, p38, and ERK phosphorylation; SMAD3 and AP-1 activation; and subsequent CTGF expression in human lung fibroblasts. Thus, MPT0E028 may be a potential drug for treating pulmonary fibrosis.

Several factors would be involved in the increase in serum N-terminal fragment CTGF level. In conclusion, serum N-terminal fragment CTGF level is a promising new biomarker for CP.

P3, N=73, Terminated, FibroGen | Trial completion date: May 2024 --> Dec 2023 | Active, not recruiting --> Terminated; Study did not meet its primary endpoint.

Summarizing the CTGF-targeting and -inhibitory drugs is also beneficial for the analysis of the efficacy, applications, and limitations of these drugs in different disease models. Therefore, we reviewed the CTGF structure, the regulatory mechanisms in various diseases, and drug development in order to provide more references for future drug discovery.

In conclusion, low CTGF expression was associated with a significantly worse OS in patients with diffuse-type GC. These data indicated that CTGF, and its control by the Hippo pathway, may be considered potential treatment targets in diffuse-type GC.

Remarkably, CCN2 expression did not correlate with fibrosis or other disease parameters such as platelet count or thrombovascular events, neither in this subgroup nor in the whole study group. This suggests that in BM of MPN patients other, CCN2-independent pathways (such as noncanonical TGF-β signaling) may be more important for the development of fibrosis.

P3, N=284, Active, not recruiting, FibroGen | Trial completion date: Dec 2023 --> Apr 2024 | Trial primary completion date: Dec 2023 --> Apr 2024

P2, N=22, Completed, Olix Pharmaceuticals, Inc. | Phase classification: P2a --> P2

This study provides a characterization of the signaling pathways and effector genes involved in CAFs activation, and strategies that could effectively inhibit it in the context of GC. Video Abstract.

P3, N=356, Terminated, FibroGen | Trial completion date: May 2024 --> Aug 2023 | Active, not recruiting --> Terminated; Study did not meet its primary endpoint.

Histone deacetylase (HDAC) inhibitors diminish carcinogenesis, metastasis, and cancer cell proliferation by inducing death in cancer cells. Since combination treatment exhibits much higher anti-tumor potential than 5-FU alone, panobinostat effectively potentiates the anti-tumor efficacy of 5-FU. As a result, it is believed that panobinostat and 5-FU combination therapy will be useful as supplemental chemotherapy in the future.

In summary, our findings propose CTGF as a potential prognostic marker for guiding TNBC treatment and suggest kahweol as a promising antitumor compound capable of regulating CTGF expression to suppress cell motility in TNBC. These insights hold promise for the development of targeted therapies and improved clinical outcomes for TNBC patients.

This study elucidates a novel driving PIEZO1-YAP1-CTGF force, which opens a novel therapeutic avenue to block the transformation from precancerous lesions to GC. H. pylori-NF-κB activates the PIEZO1-YAP1-CTGF axis to remodel the GC microenvironment by promoting CAF infiltration. Targeting PIEZO1-YAP1-CTGF plus chemotherapy might serve as a potential therapeutic option to block GC progression and peritoneal metastasis.

P3, N=372, Terminated, FibroGen | Trial completion date: Apr 2025 --> Sep 2023 | Active, not recruiting --> Terminated | Trial primary completion date: Mar 2024 --> Sep 2023; Sponsor Decision

P2a, N=22, Completed, Olix Pharmaceuticals, Inc. | Active, not recruiting --> Completed | Trial primary completion date: Jun 2022 --> Jan 2023

P1, N=64, Completed, Pieris Australia Pty Ltd | Recruiting --> Completed

We identified CTGF is an important regulator of the epithelial phenotype, and its loss is associated with the early cellular modifications required for EMT. We describe a novel role for CTGF, regulating cytoskeleton and the extracellular matrix interactions necessary for the conservation of epithelial structure and function. These findings provide a new window into understanding the early stages of mesenchymal transformation.

P2, N=21, Terminated, FibroGen | Active, not recruiting --> Terminated; Sponsor Decision

CTGF was associated with tumor-stroma crosstalk in BTC. CTGF activated stromal SPARC expression, which promoted tumor progression, particularly at the invasion front. SPARC expression at the invasion front after NAC-RT may serve as a prognosis predictor.

Mechanistically, circTGFBR2 delivered into HCC cells via exosomes serves as a competing endogenous RNA by binding miR-205-5p to facilitate ATG5 expression and enhance autophagy in HCC cells, resulting in resistance to starvation. Thus, we revealed that circTGFBR2 is a novel tumor promoter circRNA in hepatocytic exosomes and promotes HCC progression by enhancing ATG5-mediated protective autophagy via the circTGFBR2/miR-205-5p/ATG5 axis, which may be a potential therapeutic target for HCC.

No abstract available

Our findings reveal the function of the LINC02754/E2F1/PP1A/YAP1 axis in hormone receptor-positive breast cancer and provide new insight into hormone receptor-positive breast cancer progression. AVAILABILITY OF SUPPORTING DATA: All data included in this study are available upon request by contact with the corresponding author.

We show that glutamine restriction, by removing glutamine from the medium or treatment with inhibitors that attenuate glutamine uptake (V-9302) or conversion to glutamate (CB-839), markedly reduces mesothelioma cell proliferation, spheroid formation, invasion, and migration...These changes are observed in both cells and tumors. These findings indicate that mesothelioma is a glutamine addicted cancer, show that glutamine depletion attenuates YAP1/TEAD signaling and tumor growth, and suggest that glutamine restriction may be useful as a mesothelioma treatment strategy.

Pts were randomized 1:1 to pam+investigator’s choice CT (gemcitabine 1,000 mg/m2+nab-paclitaxel 125 mg/m2; or either FOLFIRINOX [5-fluoruracil 400 mg/m2+folinic acid/leucovorin 400 mg/m2; 5-fluoruracil 2,400 mg/m2; irinotecan 180 mg/m2; oxaliplatin 85 mg/m2; or mFOLFIRINOX [folinic acid/leucovorin 400 mg/m2; 5-fluoruracil 2,400 mg/m2; irinotecan 180 mg/m2; oxaliplatin 85 mg/m2]), or CT+PBO, then stratified by unreconstructable disease (yes/no) and geographic region...LAPIS enrollment is complete (N=284). Study completion is estimated for early 2024.

Transcript levels of collagen 1A1, fibronectin 1, matrix metalloproteinase-2, cyclin E2, and BCL-2-associated X protein/B-cell lymphoma 2 ratio were strongly correlated with TG1 mRNA expression, whereas TG2 expression correlated strongly with CTGF mRNA abundance. These findings support a functional and signalling role for TG1 and TG2 from fibroblasts in regulating key processes underlying myocardial ECM homeostasis and dysregulation, suggesting that these isoforms could be potential and promising targets for the development of cardiac fibrosis therapies.

YAP1 inhibitor administration counteracted ADAM12's function in promoting CRC cell growth, migration, invasion and increasing CTGF, Cyr61 and Birc5 expression. Implications: Our study indicates that ADAM12 facilitates CRC progression through suppressing Hippo pathway activity, and that ADAM12 is the candidate therapeutic target and prognostic biomarker for CRC patients.

In some model systems, CCN1 and CCN2 play key roles in LPA/S1P-induced cell migration and proliferation. In this way, an extracellular signal (LPA or S1P) can activate GPCR-mediated intracellular signaling to induce the production of extracellular modulators (CCN1 and CCN2) that in turn initiate another round of intracellular signaling.

In this new model, an additive degeneration could be noted in optic nerves as well as in the number of RGCs. These results suggest a potential additive role of high IOP and immune factors in glaucoma development, which will aid for understanding this multifactorial disease more precisely in the future.

Furthermore, co-culture with rhCTGF reversed the si-PVT1-induced changes in the expression of EMT-associated proteins. In conclusion, lncRNA PVT1 promotes the proliferation, migration, invasiveness and EMT process of ovarian cancer cells, and CTGF contributes to the effect of lncRNA PVT1.

This is the first study to demonstrate that verteporfin-mediated inhibition of YAP leads to diminished tumorigenicity in lung and breast spinal metastatic cancer cells. Targeting of YAP with verteporfin offers promising results that could be translated to human clinical trials.

Inhibition of TEAD binding to YAP1 in mammalian cells was also observed. Several compounds inhibited the cell viability of sarcoma, hepatocellular carcinoma, glioblastoma, and breast cancer cells with single-digit micromolar IC values.