Related Experiment Video

Updated: Jun 20, 2026

Induction of Invasive Transitional Cell Bladder Carcinoma in Immune Intact Human MUC1 Transgenic Mice: A Model for Immunotherapy Development
11:02

Induction of Invasive Transitional Cell Bladder Carcinoma in Immune Intact Human MUC1 Transgenic Mice: A Model for Immunotherapy Development

Published on: October 30, 2013

SIP1 protein protects cells from DNA damage-induced apoptosis and has independent prognostic value in bladder cancer

A Emre Sayan1, Thomas R Griffiths, Raj Pal

  • 1Department of Cancer Studies and Molecular Medicine, University of Leicester, Leicester LE2 7XL, United Kingdom.

Proceedings of the National Academy of Sciences of the United States of America
|August 27, 2009
PubMed

Insights

The epithelial-mesenchymal transition (EMT) protein SIP1 is a poor prognostic factor in bladder cancer. SIP1 promotes metastasis and protects cells from apoptosis, suggesting it as a therapeutic target.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Epithelial-mesenchymal transition (EMT) drives cancer metastasis.
  • ZEB1 and ZEB2 (SIP1) proteins regulate EMT by inhibiting E-cadherin transcription.
  • The in vivo relevance of ZEB1 and SIP1 in human cancers, particularly bladder cancer, requires further investigation.

Purpose of the Study:

  • To comparatively analyze ZEB1 and SIP1 protein expression in bladder cancer cell lines and patient specimens.
  • To evaluate the prognostic significance of SIP1 and ZEB1 in bladder cancer patients.
  • To investigate the functional role of SIP1 in cellular response to DNA damage and apoptosis.

Main Methods:

  • Comparative analysis of ZEB1 and SIP1 protein expression in bladder cancer cell lines.
  • Assessment of ZEB1 and SIP1 protein levels in bladder cancer patient tissues.
  • In vitro studies on UV- and cisplatin-induced apoptosis and DNA damage response in cells with varying SIP1 levels.

Main Results:

  • ZEB1 was detected in E-cadherin-negative bladder cancer cell lines, correlating with high cell motility.
  • SIP1 was rarely detected in cultured carcinoma cells but was an independent predictor of poor prognosis in radiotherapy-treated bladder cancer patients.
  • SIP1 conferred resistance to UV- and cisplatin-induced apoptosis independent of cell cycle arrest or E-cadherin status, with reduced ATM/ATR target phosphorylation.

Conclusions:

  • SIP1, not E-cadherin status, is a significant prognostic marker in bladder cancer.
  • SIP1's anti-apoptotic function and link to genetic instability suggest its role in metastasis and potential as a therapeutic target.
  • The EMT pathway's nature, rather than E-cadherin deregulation alone, is critical for bladder cancer progression and patient survival.

Related Concept Videos

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...
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...
DNA Damage can Stall the Cell Cycle02:36

DNA Damage can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
DNA Damage Can Stall the Cell Cycle02:36

DNA Damage Can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
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...