Related Experiment Video

Updated: Mar 14, 2026

Monitoring Hippo Signaling Pathway Activity Using a Luciferase-based Large Tumor Suppressor LATS Biosensor
07:16

Monitoring Hippo Signaling Pathway Activity Using a Luciferase-based Large Tumor Suppressor LATS Biosensor

Published on: September 13, 2018

20.8K

α3β1 Integrin Suppresses Prostate Cancer Metastasis via Regulation of the Hippo Pathway

Afshin Varzavand1, Will Hacker2, Deqin Ma3

  • 1Department of Biology, Holden Comprehensive Cancer Center, University of Iowa, Iowa City, Iowa.

Cancer Research
|September 30, 2016
PubMed

Insights

Loss of alpha-3-beta-1 integrin promotes prostate cancer metastasis by disrupting Abl kinase and Hippo pathway signaling. This finding suggests new therapeutic strategies targeting integrin expression in metastatic prostate cancer.

Area of Science:

  • Integrin signaling in cancer biology
  • Molecular mechanisms of cancer metastasis
  • Prostate cancer research

Background:

  • Current anticancer strategies targeting integrins have limited success.
  • The role of integrins in suppressing tumor progression is not fully understood.
  • Alpha-3-beta-1 integrin (α3β1) is frequently downregulated in prostate cancers.

Purpose of the Study:

  • To investigate the mechanism by which α3β1 integrin restrains prostate cancer progression.
  • To establish an in vivo model of prostate cancer metastasis by depleting α3β1 integrin.
  • To identify potential therapeutic targets for metastatic prostate cancer based on integrin expression.

Main Methods:

  • Generation of an in vivo model of prostate cancer metastasis.
  • Analysis of signaling pathways involving α3β1 integrin, Abl kinases, and the Hippo pathway.
  • Assessment of prostate cancer cell migration, invasion, and anchorage-independent growth.

Main Results:

  • Depletion of α3β1 integrin promoted prostate cancer metastasis.
  • α3β1 integrin signals through Abl kinases to inhibit Rho GTPase activity and support Hippo pathway suppressors.
  • This pathway restrains prostate cancer migration, invasion, and anchorage-independent growth.
  • α3 integrin-deficient prostate cancers may respond to Hippo-targeted therapies.
  • Abl kinases exhibit paradoxical tumor suppressor functions in prostate cancer.

Conclusions:

  • The α3β1-Abl kinase-Hippo suppressor pathway is critical for restraining prostate cancer metastasis.
  • Targeting this pathway offers novel therapeutic strategies for metastatic prostate cancer.
  • Understanding integrin expression can guide treatment decisions for prostate cancer patients.
  • The findings may explain the limited efficacy of Abl kinase inhibitors in prostate cancer.

More Related Videos

An Orthotopic Murine Model of Human Prostate Cancer Metastasis06:48

An Orthotopic Murine Model of Human Prostate Cancer Metastasis

Published on: September 18, 2013

36.0K
Combined Use of Tail Vein Metastasis Assays and Real-Time In Vivo Imaging to Quantify Breast Cancer Metastatic Colonization and Burden in the Lungs10:32

Combined Use of Tail Vein Metastasis Assays and Real-Time In Vivo Imaging to Quantify Breast Cancer Metastatic Colonization and Burden in the Lungs

Published on: December 19, 2019

11.7K

Related Concept Videos

Activation of Integrins01:15

Activation of Integrins

Integrins bind ligands and transmit information from outside the cell to inside or vice-versa through an "outside-in signaling" or "inside-out signaling."
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...
5.4K
Integrins01:10

Integrins

Animal and protozoan cells do not have cell walls to help maintain shape and provide structural stability. Instead, these eukaryotic cells secrete a sticky mass of carbohydrates and proteins into the spaces between adjacent cells. This network of proteins and molecules is called an extracellular matrix or ECM.
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,...
5.9K
Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
3.9K
Intracellular Signaling Affects Focal Adhesions01:17

Intracellular Signaling Affects Focal Adhesions

Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
3.8K
Hedgehog Signaling Pathway02:33

Hedgehog Signaling Pathway

The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...
10.3K
Cancer Cell Migration through Invadopodia01:35

Cancer Cell Migration through Invadopodia

Invadosome is a broad category of cell surface structures with proteolytic activity that  degrades the extracellular matrix (ECM). Invadosomes are present in normal cell types, including macrophages, endothelial cells, and neurons, as well as tumor cells. Although the macrophage podosomes and tumor cell invadopodia are classified as invadosomes, they have different structures, molecular pathways, and functions. Podosomes are short structures that last for a few minutes. However,...
3.4K