Related Experiment Video

Updated: May 21, 2026

Bioluminescence Resonance Energy Transfer (BRET)-Based Assay for Measuring Interactions of CRAF with 14-3-3 Proteins in Live Cells
06:44

Bioluminescence Resonance Energy Transfer (BRET)-Based Assay for Measuring Interactions of CRAF with 14-3-3 Proteins in Live Cells

Published on: March 1, 2024

p21-Activated kinase 4 promotes prostate cancer progression through CREB

M-H Park1, H-S Lee, C-S Lee

  • 1Department of Biochemistry and Medical Research Center, Chungbuk National University College of Medicine, Cheongju, Korea.

Oncogene
|June 20, 2012
PubMed

Insights

p21-activated kinase 4 (PAK4) drives prostate cancer progression and resistance to hormone and chemotherapy. Inhibiting PAK4 may offer a new therapeutic strategy for advanced prostate cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Prostate cancer initially depends on androgens but often becomes resistant to hormone and chemotherapy.
  • Understanding resistance mechanisms is crucial for developing effective treatments.

Purpose of the Study:

  • To investigate the role of p21-activated kinase 4 (PAK4) in prostate cancer progression and resistance.
  • To identify the activation mechanism and downstream pathways of PAK4 in prostate cancer.

Main Methods:

  • Investigated PAK4 activation using protein kinase A (PKA) inhibitors and cAMP.
  • Analyzed PAK4 interaction with PKA and phosphorylation at S474.
  • Utilized stable knockdown of PAK4 in prostate cancer cell lines (PC-3, DU145) and tumor formation assays in nude mice.
  • Assessed expression of CREB and its targets (Bcl-2, cyclin A1).
  • Examined PAK4's role in cAMP-induced neuroendocrine differentiation and chemoresistance.

Main Results:

  • PAK4 activation is regulated by PKA and cAMP, with PKA directly phosphorylating PAK4 at S474.
  • Activated PAK4 enhances CREB transcriptional activity.
  • PAK4 knockdown inhibits tumor formation in mice and decreases expression of CREB and its targets.
  • PAK4 promotes cAMP-induced neuroendocrine differentiation and enhances survival during chemotherapy, reducing apoptosis.

Conclusions:

  • PAK4 plays a significant role in prostate cancer progression towards hormone and chemo-resistance.
  • PAK4 activation involves PKA-mediated phosphorylation.
  • PAK4 influences key pathways including CREB signaling and neuroendocrine differentiation.
  • PAK4 represents a potential therapeutic target for advanced prostate cancer.

More Related Videos

Fluorescence-based Monitoring of PAD4 Activity via a Pro-fluorescence Substrate Analog08:37

Fluorescence-based Monitoring of PAD4 Activity via a Pro-fluorescence Substrate Analog

Published on: November 5, 2014

Related Concept Videos

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...
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...
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...
Abnormal Proliferation02:23

Abnormal 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...
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...
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...