Related Experiment Video

Updated: Jul 5, 2025

A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
07:25

A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer

Published on: March 6, 2018

13.1K

TNIK drives castration-resistant prostate cancer via phosphorylating EGFR

Jianing Guo1, Jiaming Liang2, Youzhi Wang2

  • 1Department of Pathology, The Second Hospital of Tianjin Medical University, Tianjin 300211, China.

Iscience
|January 16, 2024
PubMed

Insights

Androgen receptor (AR) normally suppresses Traf2- and Nck-interacting kinase (TNIK) in prostate cancer. After androgen deprivation therapy (ADT), TNIK promotes castration-resistant prostate cancer (CRPC) by activating EGFR signaling.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Genetics

Background:

  • Castration-resistant prostate cancer (CRPC) development involves complex genetic and epigenetic factors.
  • Traf2- and Nck-interacting kinase (TNIK), a serine/threonine kinase, is linked to tumor proliferation and poor prognosis.
  • Microarray analysis indicated significantly elevated TNIK expression in CRPC.

Purpose of the Study:

  • To investigate the functional role of TNIK in CRPC progression.
  • To elucidate the regulatory relationship between androgen receptor (AR) and TNIK expression.
  • To understand how TNIK contributes to CRPC development via signaling pathways.

Main Methods:

  • Gene expression analysis using microarrays.
  • Investigation of AR binding and epigenetic modifications (H3K27me3).
  • Cellular assays to assess TNIK's role in EGFR signaling activation and CRPC progression.

Main Results:

  • AR suppresses TNIK gene transcription by forming a complex with H3K27me3 in prostate cancer cells.
  • Androgen deprivation therapy (ADT) leads to reduced AR levels, allowing TNIK upregulation.
  • TNIK is recruited to activate epidermal growth factor receptor (EGFR) signaling through phosphorylation, promoting CRPC progression.

Conclusions:

  • AR acts as a repressor of TNIK transcription.
  • TNIK promotes CRPC progression by activating the EGFR pathway via phosphorylation.
  • Targeting TNIK presents a potential therapeutic strategy for CRPC.
Keywords:
BiochemistryCancerMolecular biology

More Related Videos

Murine Prostate Micro-dissection and Surgical Castration08:49

Murine Prostate Micro-dissection and Surgical Castration

Published on: May 11, 2016

45.7K
Virus Delivery of CRISPR Guides to the Murine Prostate for Gene Alteration06:21

Virus Delivery of CRISPR Guides to the Murine Prostate for Gene Alteration

Published on: April 27, 2018

8.7K

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...
6.5K
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...
3.8K
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...
3.6K
Receptor Tyrosine Kinases01:26

Receptor Tyrosine Kinases

Receptor tyrosine kinases or RTKs are membrane-bound receptors that phosphorylate specific tyrosine on protein substrates. RTKs regulate cellular growth, differentiation, survival, and migration. They contain an extracellular ligand binding domain, a transmembrane domain, and a cytosolic tail with intrinsic kinase activity. Several extracellular signaling molecules activate RTKs in one or more ways and relay the signal downstream. Ligands such as platelet-derived growth factor (PDGF) or...
13.0K
Enzyme-linked Receptors01:00

Enzyme-linked Receptors

Enzyme-linked receptors are proteins that act as both receptor and enzyme, activating multiple intracellular signals. This is a large group of receptors that include the receptor tyrosine kinase (RTK) family. Many growth factors and hormones bind to and activate the RTKs.
Neurotrophin (NT) receptors are a family of RTKs, including trkA, trkB, and trkC (tropomyosin-related kinase) receptors. TrkA is specific for nerve growth factor (NGF), neurotrophin-6, and neurotrophin-7. TrkB binds...
78.5K
The Ras Gene02:38

The 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...
6.2K