Anchorage-independent growth is the most significant hallmark of cell transformation, which has an intimate relevance to cancer. Anchorage or adhesion physically links cells to the extracellular matrix and allows the transmission of external mechanical cues to intracellular signaling machineries. Transformation involves acquiring the ability to proliferate without requiring mechanically initiated signal transduction, known as mechanotransduction. A number of signaling and cytoskeletal molecules are located at focal adhesions. Src and its related proteins, including p130Cas, localize to adhesion sites, where their functions can be mechanically regulated. In addition, the aberrant activation and expression of Src and p130Cas are linked to transformation and malignancy both in vitro and in vivo. These findings shed light on the importance of mechanotransduction in tumorigenesis and the regulation of cancer progression and also provide insights into the mechanical aspects of cancer signaling.
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http://dx.doi.org/10.1177/1947601912461443 | DOI Listing |
Int Immunopharmacol
November 2024
Department of General Practice, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, China; Wenzhou Key Laboratory of Precision General Practice and Health Management, Wenzhou 325000, China; South Zhejiang Institute of Radiation Medicine and Nuclear Technology, Wenzhou 325014, China; Department of General Practice, Taizhou Women and Children's Hospital of Wenzhou Medical University, Taizhou 318001, China. Electronic address:
Pulmonary fibrosis (PF) results from excessive extracellular matrix (ECM) deposition and tissue remodeling after activation of fibroblasts into myofibroblasts. Abnormally deposited fibrotic ECM, in turn, promotes fibroblast activation and accelerates loss of lung structure and function. However, the molecular mediators and exact mechanisms by which fibrotic ECM promotes fibroblast activation are unclear.
View Article and Find Full Text PDFMethods Enzymol
June 2024
Department of Pediatrics, Children's Mercy Kansas City and University of Missouri Kansas City School of Medicine, Kansas City, MO, United States.
Protein-protein interactions between SH2 domains and segments of proteins that include a post-translationally phosphorylated tyrosine residue (pY) underpin numerous signal transduction cascades that allow cells to respond to their environment. Dysregulation of the writing, erasing, and reading of these posttranslational modifications is a hallmark of human disease, notably cancer. Elucidating the precise role of the SH2 domain-containing adaptor proteins Crk and CrkL in tumor cell migration and invasion is challenging because there are no specific and potent antagonists available.
View Article and Find Full Text PDF3 Biotech
November 2023
Department of Biology, Faculty of Science, University of Guilan, Rasht, Iran.
Colon cancer is the fifth leading cause of cancer-related deaths worldwide. Stem cells have unique characteristics and are considered as a novel therapeutic platform for cancer. Sugen Kinase 269 (SgK269) is considered as an oncogenic scaffolding pseudo kinase which governs the rearranging of the cytoskeleton, cellular motility, and invasion.
View Article and Find Full Text PDFElife
July 2023
Fred Hutchinson Cancer Center, Seattle, United States.
Integrin-mediated cell attachment rapidly induces tyrosine kinase signaling. Despite years of research, the role of this signaling in integrin activation and focal adhesion assembly is unclear. We provide evidence that the Src-family kinase (SFK) substrate Cas (Crk-associated substrate, p130Cas, BCAR1) is phosphorylated and associated with its Crk/CrkL effectors in clusters that are precursors of focal adhesions.
View Article and Find Full Text PDFAm J Cancer Res
June 2022
Institute of Biomedical Sciences, National Chung Hsing University Taichung, Taiwan.
The tyrosine kinase Src plays an essential role in the progression of many cancers and is involved in several epidermal growth factor receptor (EGFR)-mediated signalling pathways. To improve the efficacy of lung cancer treatments, this study aimed to identify novel compounds that can disrupt the Src-EGFR interaction and that are less dependent on EGFR status with wild-type and mutations than other compounds. We used the Src pY419 ELISA as the platform to screen a compound library of more than 400 plant-derived active ingredients and identified peruvoside as a candidate Src-EGFR crosstalk inhibitor.
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