TrkB/BDNF Signaling Could Be a New Therapeutic Target for Pancreatic Cancer

Abstract

Background/Aim: Tropomyosin-related kinase B (TrkB)/brain-derived neurotrophic factor (BDNF) signaling plays a role in inducing malignant phenotypes in several aggressive types of cancers. To create a conclusive therapy targeting TrkB/BDNF signaling in solid refractory cancers, the biological significance of TrkB/BDNF signaling was analyzed in pancreatic ductal adenocarcinoma (PDAC) cells. Materials and Methods: Three PDAC cell lines were used as target cells to investigate proliferation and invasiveness. Small interfering RNA (siRNA) and the TrkB tyrosine kinase inhibitor k252a were used as TrkB/BDNF signaling inhibitors. Results: All PDAC cell lines expressed TrkB and BDNF. When TrkB and BDNF were inhibited by siRNA or k252a, the invasiveness of PANC-1 and SUIT-2 cells significantly decreased. When TrkB was inhibited by siRNA or k252a, proliferation was significantly inhibited in PDAC cells. Conclusion: TrkB/BDNF signaling may be a new therapeutic target for PDAC. Therapies targeting TrkB/BDNF signaling may be a conclusive cancer therapy for refractory solid cancer.

An oxidative stress-related signature for predicting the prognosis of liver cancer

“…Matrix metallopeptidase-9 (MMP-9) has been widely associated with cancer pathology (Huang, 2018). S100A9 is an oxidative stress gene (Saheb Sharif-Askari et al, 2021), and Lv et al (2020) found that S100A9 enhances prostate cancer cell invasion by activating TLR4/NF-κB/integrin β1/FAK signaling. Chen et al (2021) found that β-sarcoglycan (SGCB) is a prognostic metabolism-related gene in clear-cell RCC.…”

“…Brain-derived neurotrophic factor (BDNF) is a potent neurotrophic factor ( Numakawa et al, 2018 ) that promotes breast cancer cell growth and metastasis ( Tajbakhsh et al, 2017 ). Oyama et al revealed that tropomycin receptor kinase B (TrkB)/BDNF signaling could be a novel therapeutic target in pancreatic cancer ( Oyama et al, 2021 ). Liu et al (2009) found that Fas ligand (FASLG) polymorphisms were correlated with cancer risk.…”

Interference of Neuronal TrkB Signaling by the Cannabis-Derived Flavonoids Cannflavins A and B

“…Furthermore, a study uncovered a link between the ability of glioblastoma to make less invasive cancer cells around them more aggressive via the transfer of TrkB-containing exosomes, revealing this way a mechanism by which these tumours can influence their environment to promote disease progression and aggressiveness (Pinet al et., 2016), while other reports have shown that inhibition of TrkB-associated signaling may be an effective strategy to limit the formation of astrocytomas (Ni et al, 2017) as well as the survival of glioblastoma cancer cells (Pinheiro et al, 2017). Finally, emerging evidence suggest that TrkB signaling could also be a therapeutic target for other cancer types, including lung (Sinkevicius et al, 2014; Chen et al, 2016), breast (Choy et al, 2017; Contreras-Zárate et al, 2019), and pancreatic cancer (Oyama et al, 2021). Taken together, these studies suggest that targeting TrkB signaling with cannflavins may provide therapeutic benefits against these cancer types.…”

Schwann Cells in Digestive System Disorders

“…Until now, 3D imaging of PanIN lesions allowed visualisation of glial activation in an early stage of tumorigenesis and demonstrated a 5-fold increase in GFAP+ fibers [ 159 ]. Furthermore, many soluble factors of neurotrophic or axon-guiding nature such as NGF [ 147 , 160 ], brain-derived neurotrophic factor (BDNF) [ 147 , 161 ], neurotrophin 3 (NT-3) [ 147 , 162 ], glial-cell-derived neurotrophic factor (GDNF) [ 163 ], neurturin [ 164 ], artemin [ 165 , 166 ], sonic hedgehog [ 167 , 168 ], SEMA3D [ 169 ], and others are overexpressed by pancreatic tumour cells. SCs are well known to express the same factors in injury settings [ 43 ].…”