Related Experiment Video
Updated: May 13, 2026

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
Published on: October 27, 2020
Parathyroid hormone-related protein regulates integrin α6 and β4 levels via transcriptional and post-translational
Vandanajay Bhatia1, Ramanjaneya V R Mula, Miriam Falzon
1Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, TX 77555, United States.
Abstract:
Parathyroid hormone-related protein (PTHrP) enhances prostate cancer (CaP) growth and metastasis in vivo. PTHrP also increases cell survival and migration, and upregulates pro-invasive integrin α6β4 expression. We used the human CaP cell lines C4-2 and PC-3 as model systems to study the mechanisms via which PTHrP regulates α6β4 levels. We report that PTHrP regulates α6 and β4 levels via a transcriptional pathway; β4 regulation involves the NF-κB pathway. PTHrP also regulates β4 levels at the post-translational level. PTHrP inhibits caspase-3 and -7 activities. Post-translational regulation of β4 by PTHrP is mediated via attenuation of its proteolytic cleavage by these caspases. Since α6 dimerizes with β4, increased β4 levels result in elevated α6 levels. Suppressing β4 using siRNA attenuates the effect of caspase inhibition on apoptosis and cell migration. These results provide evidence of a link between PTHrP, integrin α6β4 levels as a function of caspase activity, and cell survival and migration. Targeting PTHrP in CaP cancer, thereby reversing the effect on caspase activity and α6β4 levels, may thus prove therapeutically beneficial.
More Related Videos
Related Concept Videos
Intracellular Signaling Affects Focal Adhesions
Some...
Activation of Integrins
In "outside-in signaling," external factors in the extracellular space bind to exposed ligand binding sites on integrins. This causes the inactive protein to undergo a conformational change to become active. Integrins are often clustered on the cell membrane. Repetitive and regularly spaced ligand binding events provide an effective stimulus.
TGF - β Signaling Pathway
Integrins
Some ECM proteins assemble into a basement membrane to which the remaining components adhere. Proteoglycans typically form the bulk of the ECM while fibrous proteins, like collagen,...
Regulation of Angiogenesis and Blood Supply
Hormones and Bone Tissue
Hormones That Influence Osteoblasts and/or Maintain the Matrix
Several hormones are necessary for controlling bone growth and maintaining the bone matrix. The pituitary gland secretes growth hormone (GH), which, as its name implies, controls bone growth. This happens in several ways: first, it triggers chondrocyte...

