Related Experiment Video

Updated: Aug 7, 2026

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death
09:18

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death

Published on: December 27, 2016

Epidermal growth factor protects prostate cancer cells from apoptosis by inducing BAD phosphorylation via redundant

Konduru S R Sastry1, Yelena Karpova, George Kulik

  • 1Department of Cancer Biology, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, USA.

The Journal of Biological Chemistry
|July 19, 2006
PubMed

Insights

Receptor tyrosine kinases protect prostate cancer cells from apoptosis via two distinct pathways. Simultaneous inhibition of both Ras/MEK and Rac/PAK1 signaling is required to block epidermal growth factor-induced survival.

Area of Science:

  • Oncology
  • Cell Biology
  • Molecular Biology

Background:

  • Receptor tyrosine kinases (RTKs) confer resistance to apoptosis in cancer cells.
  • Mechanisms underlying RTK-mediated anti-apoptosis, particularly resistance to phosphatidylinositol 3'-kinase/Akt and Ras/MEK inhibition, remain unclear.
  • Prostate cancer cells exhibit resistance to apoptosis, necessitating investigation into survival pathways.

Purpose of the Study:

  • To elucidate the signaling pathways responsible for epidermal growth factor (EGF)-induced protection from apoptosis in prostate cancer cells.
  • To identify the specific molecular targets and mechanisms of anti-apoptotic signaling downstream of RTKs.
  • To understand the redundancy in anti-apoptotic signaling pathways for therapeutic implications.

Main Methods:

  • Utilized prostate cancer cell lines.
  • Investigated signaling cascades activated by epidermal growth factor (EGF).
  • Analyzed protein phosphorylation events, specifically on the pro-apoptotic protein BAD at Ser112 and Ser136, using molecular biology techniques.

Main Results:

  • EGF activates two distinct anti-apoptotic signaling pathways in prostate cancer cells.
  • One pathway involves Ras/MEK signaling, leading to BAD phosphorylation at Ser112.
  • A second, parallel pathway involves Rac/PAK1 signaling, causing BAD phosphorylation at Ser136.
  • Each pathway independently confers protection from apoptosis.

Conclusions:

  • Both Ras/MEK and Rac/PAK1 pathways must be simultaneously inhibited to block EGF-dependent cell survival.
  • The identified redundant anti-apoptotic signaling pathways highlight the complexity of targeting cancer cell survival.
  • Therapeutic strategies against anti-apoptotic mechanisms in cancer should consider pathway redundancy.

More Related Videos

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells06:54

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells

Published on: October 27, 2020

Isolation, Culture, and Characterization of Prostate Cancer-Associated Fibroblasts09:43

Isolation, Culture, and Characterization of Prostate Cancer-Associated Fibroblasts

Published on: August 1, 2025

Related Concept Videos

Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
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...
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...
Amplifying Signals via Enzymatic Cascade01:22

Amplifying Signals via Enzymatic Cascade

When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze the...
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...
The Intrinsic Apoptotic Pathway01:31

The 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...