Several lines of evidence suggest that gastrin and the CCK-2 receptor (CCK2R) could contribute to pancreatic carcinogenesis by modulating processes such as proliferation, cell adhesion or migration. In the current study, we used a 'cancer gene array' and identified beta1-integrin subunit as a new gastrin-regulated gene in human pancreatic cancer cells. We also demonstrated that Src family kinases and the phosphatidylinositol-3-kinase (PI-3-kinase) pathway play a crucial role in the expression of beta1-integrin induced by gastrin. Our results also showed that gastrin modulates cell-substrate adhesion via beta1-integrin. Indeed, using blocking anti-beta1-integrin monoclonal antibodies, we completely reversed the increase in cell-substrate adhesion induced by gastrin. In addition, we observed that in response to gastrin, beta1-integrin is tyrosine phosphorylated by Src family kinases and associates with paxillin, a scaffold protein involved in focal adhesion and integrin signalling. This mechanism might be involved in gastrin-induced cell adhesion. Moreover, we showed in vivo that targeted CCK2R expression in the pancreas of Elas-CCK2 mice leads to the overexpression of beta1-integrin. This process may contribute to pancreatic tumour development observed in these transgenic animals.
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http://dx.doi.org/10.1038/sj.onc.1209484 | DOI Listing |
ACS Chem Biol
January 2025
Department of Pediatric Dentistry, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University, and Shandong Key Laboratory of Oral Tissue Regeneration, Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration, Shandong Provincial Clinical Research Center for Oral Diseases, Jinan 250012, China.
Chronic kidney fibrosis poses a significant global health challenge with effective therapeutic strategies remaining elusive. While cell-extracellular matrix (ECM) interactions are known to drive fibrosis progression, the specific role of focal adhesions (FAs) in kidney fibrosis is not fully understood. In this study, we investigated the role of FAs in kidney tubular epithelial cell fibrosis by employing precise nanogold patterning to modulate integrin distribution.
View Article and Find Full Text PDFCytotherapy
January 2025
Regenerative Medicine Laboratory, Dr. D. Y. Patil Dental College and Hospital, Dr. D. Y. Patil Vidyapeeth, Pimpri, Pune 411018, India.
Background Aims: The clinical translation of mesenchymal stromal cell secretome (MSC-S) has been challenging owing to a lack of appropriate methods in downstream processing. Dialysis is an age-old method of protein purification by the exchange of small molecules through a semi-permeable membrane. In this study, we investigated the potential of three forms of umbilical cord-derived MSC secretome (UC-MSC-S)-native (S), dialyzed (DS), and lyophilized (LDS)-for wound healing applications.
View Article and Find Full Text PDFJ Dermatol Sci
December 2024
Department of Dermatology, University of Tokyo Graduate School of Medicine, Tokyo, Japan; Department of Dermatology, Tohoku University Graduate School of Medicine, Sendai, Japan. Electronic address:
Background: Altered Fli1 expression is associated with various autoimmune diseases, yet its impact on B cells remains unexplored.
Objective: This study investigated the direct effects of Fli1 depletion on B cell populations, focusing on age-associated B cells (ABCs).
Methods: Splenocytes of Fli1 BcKO (Cd19-Cre; Fli1) and Cd19-Cre mice were analyzed flow cytometrically.
Int J Biol Macromol
January 2025
Materials Engineering Group, Golpayegan College of Engineering, Isfahan University of Technology, Golpayegan 87717-67498, Iran.
3D printing, as a layer-by-layer manufacturing technique, enables the customization of tissue engineering scaffolds. Surface modification of biomaterials is a beneficial approach to enhance the interaction with living cells and tissues. In this research, a polylactic acid/polyethylene glycol scaffold containing 30 % bredigite nanoparticles (PLA/PEG/B) was fabricated utilizing fused deposition modeling (FDM) 3D printing.
View Article and Find Full Text PDFEur J Med Chem
January 2025
State Key Laboratory of Chemical Biology, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, #345 Lingling Rd, Shanghai, 200032, China. Electronic address:
The pseudokinase HER3 emerges as a promising anti-cancer target, especially for HER2-driven breast cancer and EGFR-mediated non-small cell lung cancer. However, it is challenging to target HER3 by ATP-competitive small molecules because HER3 is catalytically impaired. Herein, we report the discovery of a series of HER3 degraders by connecting a HER3 binder bosutinib with a hydrophobic tag adamantane.
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