Oncogenic MSH6-CXCR4-TGFB1 Feedback Loop: A Novel Therapeutic Target of Photothermal Therapy in Glioblastoma Multiforme

Chen, Yaodong; Liu, Pengfei; Sun, Peng; Jiang, Jian; Zhu, Yuanbo; Dong, Tianxiu; Cui, Yingzhe; Tian, Yuan; An, Tingting; Zhang, Jiuwei; Li, Zizhuo; Yang, Xiuhua

doi:10.7150/thno.29987

Cited by 35 publications

(29 citation statements)

References 71 publications

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“…Interestingly, in other aggressive human tumors, such as melanoma and glioblastoma, TGFβ signaling is maintained in cancer cells, mainly through non-canonical signaling cascades (PI3K/AKT and RAS/MAPK pathways) 38 . In these tumors, canonical SMAD-dependent signaling also contributes to TGFβ pro-metastatic functions, particularly by upregulating genes involved in epithelial to mesenchymal transition, such as SLUG and SNAIL 39 , 40 . Here, we found that TGFBI signaling follows an alternative, non-canonical pathway that in some CRC cell lines relies on p38.…”

Section: Discussionmentioning

confidence: 99%

Metastatic colorectal cancer cells maintain the TGFβ program and use TGFBI to fuel angiogenesis

Chiavarina¹,

Costanza²,

Ronca³

et al. 2021

Theranostics

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Section: Discussionmentioning

confidence: 99%

Metastatic colorectal cancer cells maintain the TGFβ program and use TGFBI to fuel angiogenesis

Chiavarina¹,

Costanza²,

Ronca³

et al. 2021

Theranostics

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“…As a growth factor, TGF- β 1 exerts biological functions regulating cell proliferation, differentiation, apoptosis, and immunity. TGF- β 1 induces tumor cell apoptosis and inhibits tumor growth by regulating the downstream signal transduction molecule Smad in the early stages of tumor development [ 55 , 56 ]. With further development of the tumor, gene mutations in the TGF- β 1 receptor or its downstream Smad pathway accumulate in tumor cells, resulting in the weakening of TGF- β 1 inhibition [ 55 ].…”

Section: Discussionmentioning

confidence: 99%

“…The activation of the TGF- β 1 receptor promotes EMT, and polarized epithelial cells can be transformed into active stromal capable of invasion and migration. This process is a crucial stage of tumor occurrence, growth, and metastasis [ 56 , 57 ]. TGF- β 1 is a chemokine that can attract macrophages and fibroblasts and cause the release of bFGF, PDGF, TNF-a, and other vasoactive factors, thus promoting angiogenesis and inducing tumor metastasis [ 24 , 56 ].…”

Section: Discussionmentioning

confidence: 99%

Preparation, Biosafety, and Cytotoxicity Studies of a Newly Tumor-Microenvironment-Responsive Biodegradable Mesoporous Silica Nanosystem Based on Multimodal and Synergistic Treatment

Zhang

et al. 2020

Oxidative Medicine and Cellular Longevity

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Patients with triple negative breast cancer (TNBC) often suffer relapse, and clinical improvements offered by radiotherapy and chemotherapy are modest. Although targeted therapy and immunotherapy have been a topic of significant research in recent years, scientific developments have not yet translated to significant improvements for patients with TNBC. In view of these current clinical treatment shortcomings, we designed a silica nanosystem (SNS) with Nano-Ag as the core and a complex of MnO2 and doxorubicin (Dox) as the surrounding mesoporous silica shell. This system was coated with anti-PD-L1 to target the PD-L1 receptor, which is highly expressed on the surface of tumor cells. MnO2 itself has been shown to act as chemodynamic therapy (CDT), and Dox is cytotoxic. Thus, the full SNS system presents a multimodal, potentially synergistic strategy for the treatment of TNBC. Given potential interest in the clinical translation of SNS, the biological safety and antitumor activity of SNS were evaluated in a series of studies that included physicochemical characterization, particle stability, blood compatibility, and cytotoxicity. We found that the particle size and zeta potential of SNS were 94.6 nm and -22.1 mV, respectively. Ultraviolet spectrum analysis showed that Nano-Ag, Dox, and MnO2 were successfully loaded into SNS, and the drug loading ratio of Dox was about 10.2%. Stability studies found that the particle size of SNS did not change in different solutions. Hemolysis tests showed that SNS, at levels far exceeding the anticipated physiologic concentrations, did not induce red blood cell lysis. Further in vitro and in vivo experiments found that SNS did not activate platelets or cause coagulopathy and had no significant effects on the total number of blood cells or hepatorenal function. Cytotoxicity experiments suggested that SNS significantly inhibited the growth of tumor cells by damaging cell membranes, increasing intracellular ROS levels, inhibiting the release of TGF-β1 cytokines by macrophages, and inhibiting intracellular protein synthesis. In general, SNS appeared to have favorable biosafety and antitumor effects and may represent an attractive new therapeutic approach for the treatment of TNBC.

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“…USI can also be evaluated systematically with multi-parameters such as Doppler and elastography (43). The ultrasound scan mode in this experiment included B-mode, CDFI, CPA and USE.…”

Section: Cvb-d Inhibition On the Growth Of Crc Xenograft Tumors In Numentioning

confidence: 99%

Cyclovirobuxine D inhibits colorectal cancer tumorigenesis via the CTHRC1‑AKT/ERK‑Snail signaling pathway

et al. 2020

Self Cite

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Cyclovirobuxine D (CVB-D) is an alkaloid, which is mainly derived from Buxus microphylla. It has been reported that CVB-D has positive effects on breast cancer, gastric cancer and other malignant tumors. However, to the best of our knowledge, there are no reports regarding the effects of CVB-D on colorectal cancer (CRC). The purpose of the present study was to determine the anticancer effects of CVB-D and further elucidate its molecular mechanism(s). DLD-1 and LoVo cell lines were selected to evaluate the antitumor effect of CVB-D. Cytotoxicity, viability and proliferation were evaluated by the MTT and colony formation assays. Flow cytometry was used to detect the effects on apoptosis and the cell cycle in CVB-D-treated CRC cells. The migration and invasion abilities of CRC cells were examined by wound healing and Transwell assays. In addition, RNA sequencing, bioinformatics analysis and western blotting were performed to investigate the target of drug action and clarify the molecular mechanisms. A xenograft model was established using nude mice, and ultrasound was employed to assess the preclinical therapeutic effects of CVB-D in vivo. It was identified that CVB-D inhibited the proliferation, migration, stemness, angiogenesis and epithelial-mesenchymal transition of CRC cells, and induced apoptosis and S-phase arrest. In addition, CVB-D significantly inhibited the growth of xenografts. It is notable that CVB-D exerted anticancer effects in CRC cells partly by targeting collagen triple helix repeat containing 1 (CTHRC1), which may be upstream of the AKT and ERK pathways. CVB-D exerted anticancer effects through the CTHRC1-AKT/ERK-Snail signaling pathway. Targeted therapy combining CTHRC1 with CVB-D may offer a promising novel therapeutic approach for CRC treatment.

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Oncogenic MSH6-CXCR4-TGFB1 Feedback Loop: A Novel Therapeutic Target of Photothermal Therapy in Glioblastoma Multiforme

Cited by 35 publications

References 71 publications

Metastatic colorectal cancer cells maintain the TGFβ program and use TGFBI to fuel angiogenesis

Metastatic colorectal cancer cells maintain the TGFβ program and use TGFBI to fuel angiogenesis

Preparation, Biosafety, and Cytotoxicity Studies of a Newly Tumor-Microenvironment-Responsive Biodegradable Mesoporous Silica Nanosystem Based on Multimodal and Synergistic Treatment

Cyclovirobuxine D inhibits colorectal cancer tumorigenesis via the CTHRC1‑AKT/ERK‑Snail signaling pathway

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