Related Experiment Video
Updated: Aug 2, 2026
08:49
Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries
Published on: January 22, 2019
The integrin-linked kinase (ILK) suppresses anoikis
S Attwell1, C Roskelley, S Dedhar
1British Columbia Cancer Agency and Jack Bell Research Centre, Vancouver, Canada.
Oncogene
|August 19, 2000
Summary
Integrin-linked kinase (ILK) suppresses anoikis, a programmed cell death. Inhibiting ILK induces anoikis in cancer cells, suggesting ILK is a key regulator in metastasis.
Area of Science:
- Cell biology
- Molecular oncology
- Biochemistry
Background:
- Anoikis, or apoptosis induced by cell detachment, is a crucial barrier against cancer metastasis.
- While several pathways suppress anoikis, the precise mechanisms near integrin receptors remain elusive.
- Integrin-linked kinase (ILK) interacts with integrins and phosphorylates PKB/Akt, suggesting a role in anoikis suppression.
Purpose of the Study:
- To investigate the role of Integrin-linked kinase (ILK) in anoikis suppression.
- To determine if ILK activity is regulated by cell adhesion and if it impacts anoikis sensitivity.
- To explore ILK's potential as a therapeutic target in anoikis-resistant cancers.
Main Methods:
- Assessed ILK activity in adherent versus suspended SCP2 mouse mammary epithelial cells.
- Overexpressed ILK and dominant-negative ILK (ILK KD) or PKB/Akt (PKB AAA) in SCP2 cells.
- Inhibited ILK activity in anoikis-resistant human breast cancer cell lines.
- Measured anoikis using annexin V binding and caspase activation assays.
Main Results:
- ILK activity was stimulated by cell adhesion and inhibited by suspension.
- Overexpression of ILK profoundly inhibited anoikis in SCP2 cells, an effect reversed by ILK KD and PKB AAA.
- Inhibition of ILK induced anoikis in anoikis-resistant human breast cancer cell lines.
- FAK-related non-kinase (FRNK) did not reverse ILK-mediated anoikis suppression.
Conclusions:
- Integrin-linked kinase (ILK) plays a significant role in suppressing anoikis.
- ILK activity is modulated by cell-matrix interactions and directly impacts anoikis sensitivity.
- Targeting ILK may represent a viable strategy to overcome anoikis resistance in cancer metastasis.
Related Concept Videos
01:17The Extrinsic Apoptotic Pathway
The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
01:31The Intrinsic Apoptotic Pathway
Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
01:20The JAK-STAT Signaling Pathway
Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as SH2...
01:22PI3K/mTOR/AKT Signaling Pathway
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a rapamycin-insensitive companion...
01:15Activation 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 events provide an effective stimulus.
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.
01:17Intracellular 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...
Some...