Related Experiment Video
Updated: Jun 10, 2026
06:12
LPS and ATP-induced Death of PMA-differentiated THP-1 Macrophages and its Validation
Published on: May 3, 2024
p66(Shc) and Ras: controlling anoikis from the inside-out
1Department of Pathology and Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA 94143, USA. Jayanta.Debnath@ucsf.edu
Oncogene
|August 17, 2010
Summary
The adapter protein p66(Shc) plays a crucial role in anoikis (detachment-induced cell death) and metastasis suppression. It acts via an
Area of Science:
- Cell biology
- Cancer research
- Molecular oncology
Background:
- Anoikis, or detachment-induced cell death, is a crucial process that normally prevents cancer cells from spreading.
- The loss of integrin-mediated 'outside-in' survival signals is the primary mechanism understood to inhibit anoikis.
- Metastasis, the spread of cancer, relies on cancer cells evading anoikis.
Purpose of the Study:
- To investigate the role of the adapter protein p66(Shc) in anoikis and metastasis.
- To elucidate the signaling pathways by which p66(Shc) influences cell survival and proliferation in response to attachment.
- To identify novel mechanisms regulating anoikis beyond traditional 'outside-in' signaling.
Main Methods:
- Cell culture models to study anoikis.
- Western blotting and immunoprecipitation to analyze protein interactions and signaling.
- Gene silencing techniques (e.g., siRNA) to assess the function of p66(Shc).
- Ras activation assays and proliferation assays.
Main Results:
- p66(Shc) promotes anoikis and suppresses metastasis.
- p66(Shc) functions through an 'inside-out' attachment sensing mechanism.
- p66(Shc) regulates anoikis via Ras-dependent control of cell proliferation and survival.
Conclusions:
- p66(Shc) is a key regulator of anoikis, acting through an 'inside-out' signaling pathway.
- Targeting p66(Shc) may offer a novel therapeutic strategy to inhibit cancer metastasis.
- This study reveals a new layer of regulation in anoikis, involving adapter proteins and 'inside-out' signaling.
Related Concept Videos
02:38The Ras Gene
The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a superfamily...
Ras is a superfamily...
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...
01:17The 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...
01:24Small GTPases - Ras and Rho
Ras and Rho are small monomeric GTPases that act downstream of receptor tyrosine kinase (RTK) and regulate various cellular processes. These GTPases switch between active and inactive states by binding to guanine nucleotides.
Three regulatory proteins control their activity:
Three regulatory proteins control their activity:
02:23Abnormal Proliferation
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
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...