Related Experiment Video

Updated: Aug 8, 2026

A Syngeneic Orthotopic Osteosarcoma Sprague Dawley Rat Model with Amputation to Control Metastasis Rate
07:31

A Syngeneic Orthotopic Osteosarcoma Sprague Dawley Rat Model with Amputation to Control Metastasis Rate

Published on: May 3, 2021

PI3-K/Akt-mediated anoikis resistance of human osteosarcoma cells requires Src activation

C Marcela Díaz-Montero1, James N Wygant, Bradley W McIntyre

  • 1Department of Surgery, Medical University of South Carolina, Charleston, SC, USA.

European Journal of Cancer (Oxford, England : 1990)
|June 9, 2006
PubMed

Insights

Src kinase activity promotes anoikis resistance in osteosarcoma cells by activating the PI3-K/Akt pathway. This study reveals a novel survival mechanism independent of FAK in non-epithelial cancers.

Area of Science:

  • Cell Biology
  • Cancer Research
  • Molecular Oncology

Background:

  • Anoikis, a form of programmed cell death, is crucial for normal tissue homeostasis.
  • Mechanisms of anoikis resistance in epithelial cells are well-studied, but less is known for non-epithelial cells like sarcomas.
  • Understanding anoikis resistance pathways is vital for developing targeted cancer therapies.

Purpose of the Study:

  • To investigate the molecular mechanisms underlying anoikis resistance in human osteosarcoma SAOS-2 cells.
  • To identify key signaling pathways, such as Src, FAK, and PI3-K/Akt, involved in anoikis resistance in non-epithelial cancer cells.

Main Methods:

  • Analysis of Src, FAK, and Akt activity in anoikis-resistant and sensitive SAOS-2 cells.
  • Pharmacological inhibition of Src kinase and PI3-K (phosphatidylinositol 3-kinase) pathways.
  • Assessment of cell survival and anoikis sensitivity following pharmacological interventions.

Main Results:

  • Src kinase activity was upregulated in anoikis-resistant SAOS-2 cells.
  • Inhibition of Src restored anoikis sensitivity, while FAK dephosphorylation occurred normally.
  • The PI3-K/Akt pathway was activated in resistant cells, and its inhibition restored sensitivity; Src inhibition decreased Akt phosphorylation.

Conclusions:

  • Src kinase plays a critical role in anoikis resistance of osteosarcoma cells.
  • A survival pathway involving Src-dependent activation of PI3-K/Akt mediates anoikis resistance, independent of FAK activity.
  • Targeting the Src/PI3-K/Akt axis may represent a therapeutic strategy for osteosarcoma and potentially other non-epithelial cancers.

More Related Videos

Intratibial Osteosarcoma Cell Injection to Generate Orthotopic Osteosarcoma and Lung Metastasis Mouse Models04:25

Intratibial Osteosarcoma Cell Injection to Generate Orthotopic Osteosarcoma and Lung Metastasis Mouse Models

Published on: October 28, 2021

Related Concept Videos

PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/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...
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The JAK-STAT Signaling Pathway01:20

The 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...
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 hydroxylase and factor...
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...