Inappropriate MET tyrosine kinase receptor signaling is detected in almost all types of human cancer and contributes to malignant growth and MET dependency via proliferative and antiapoptotic activities. Independently, Tensin-4 (TNS4) is emerging as a putative oncogene in many cancer…
Distinct c-Met activation mechanisms induce cell rounding or invasion through pathways involving integrins, RhoA and HIP1 by Anja Mai et al.
Many carcinomas have acquired oncogenic mechanisms for activating c-Met, including c-Met overexpression and excessive autocrine or paracrine stimulation with hepatocyte growth factor (HGF). However, the biological outcome of c-Met activation through these distinct modes remains ambiguous. Here, we report that…
An RNAi screen identifies KIF15 as a novel regulator of the endocytic trafficking of integrin by Anastasia Eskova et al.
α2β1 integrin is one of the most important collagen-binding receptors, and it has been implicated in numerous thrombotic and immune diseases. α2β1 integrin is a potent tumour suppressor, and its downregulation is associated with increased metastasis and poor prognosis in…
Mutant p53-associated myosin-X upregulation promotes breast cancer invasion and metastasis by Antti Arjonen et al.
Mutations of the tumor suppressor TP53 are present in many forms of human cancer and are associated with increased tumor cell invasion and metastasis. Several mechanisms have been identified for promoting dissemination of cancer cells with TP53 mutations, including increased…
SHARPIN regulates uropod detachment in migrating lymphocytes by Jeroen Pouwels et al.
SHARPIN-deficient mice display a multiorgan chronic inflammatory phenotype suggestive of altered leukocyte migration. We therefore studied the role of SHARPIN in lymphocyte adhesion, polarization, and migration. We found that SHARPIN localizes to the trailing edges (uropods) of both mouse and…
Integrin-specific control of focal adhesion kinase and RhoA regulates membrane protrusion and invasion by Patricia Costa et al.
Cell invasion through extracellular matrix (ECM) is a hallmark of the metastatic cascade. Cancer cells require adhesion to surrounding tissues for efficient migration to occur, which is mediated through the integrin family of receptors. Alterations in expression levels of β1…
A ZO-1/α5β1-integrin complex regulates cytokinesis downstream of PKCε in NCI-H460 cells plated on fibronectin by Saara Hämälistö et al.
Recently, we demonstrated that integrin adhesion to the extracellular matrix at the cleavage furrow is essential for cytokinesis of adherent cells. Here, we report that tight junction protein ZO-1 (Zonula Occludens-1) is required for successful cytokinesis in NCI-H460 cells plated…
Molecular mechanism of T-cell protein tyrosine phosphatase (TCPTP) activation by mitoxantrone by Mikko Ylilauri et al.
T-cell protein tyrosine phosphatase (TCPTP) is a ubiquitously expressed non-receptor protein tyrosine phosphatase. It is involved in the negative regulation of many cellular signaling pathways. Thus, activation of TCPTP could have important therapeutic applications in diseases such as cancer and…
Integrin inactivators: balancing cellular functions in vitro and in vivo by Daniel Bouvard et al.
Integrins mediate cell-matrix and cell-cell interactions and integrate extracellular cues to the cytoskeleton and cellular signalling pathways. Integrin function on the cell surface is regulated by their activity switching such that intracellular proteins interacting with the integrin cytoplasmic domains increase…
Aneuploidy facilitates oncogenic transformation via specific genetic alterations, including Twist2 upregulation by Gunilla Högnäs et al.
Aneuploidy, deviation from the normal chromosome number, and other chromosomal aberrations are commonly observed in cancer. Integrin-mediated adhesion and dynamic turnover of adhesion sites are required for successful cytokinesis of normal adherent cells and impaired cell division can lead to…