Related Experiment Video

Updated: Jul 25, 2025

Transfer of Manipulated Tumor-associated Neutrophils into Tumor-Bearing Mice to Study their Angiogenic Potential In Vivo
08:19

Transfer of Manipulated Tumor-associated Neutrophils into Tumor-Bearing Mice to Study their Angiogenic Potential In Vivo

Published on: July 20, 2019

6.0K

Interferon signaling promotes tolerance to chromosomal instability during metastatic evolution in renal cancer

Luigi Perelli1, Federica Carbone2,3, Li Zhang2

  • 1Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. LPerelli@mdanderson.org.

Nature Cancer
|June 26, 2023
PubMed

Insights

Understanding cancer metastasis is key. This study reveals how genetic changes, like 9p21 disruption and interferon pathway alterations, drive kidney cancer spread and how interferon signaling limits aggressive tumor evolution.

Area of Science:

  • Oncology
  • Genetics
  • Cancer Biology

Background:

  • Metastatic dissemination is a critical determinant of aggressive cancers.
  • Understanding the molecular drivers of metastatic progression is essential for developing effective therapies.

Purpose of the Study:

  • To investigate the genetic alterations driving metastatic renal tumors.
  • To elucidate the role of interferon signaling in constraining aneuploid clone propagation during cancer evolution.

Main Methods:

  • In vivo CRISPR-Cas9 genome editing to generate somatic mosaic genetically engineered models.
  • Cross-species analysis of copy number variations.
  • In vitro and in vivo genomic engineering with loss-of-function studies.
  • Development of a model for partial trisomy of chromosome 21q.

Main Results:

  • Disruption of the 9p21 locus drives systemic disease through rapid acquisition of complex karyotypes.
  • Recurrent copy number variations, including 21q loss and interferon pathway dysregulation, are major drivers of metastatic potential.
  • Interferon receptor gene cluster exhibits a dosage-dependent effect in managing chromosomal instability during metastatic progression.

Conclusions:

  • Interferon signaling plays a crucial role in constraining the propagation of aneuploid clones in cancer evolution.
  • This work provides critical knowledge on the drivers of renal cell carcinoma progression.
  • Identified key molecular routes and genetic alterations contributing to metastatic dissemination in kidney cancer.

More Related Videos

A Syngeneic Mouse Model of Metastatic Renal Cell Carcinoma for Quantitative and Longitudinal Assessment of Preclinical Therapies06:38

A Syngeneic Mouse Model of Metastatic Renal Cell Carcinoma for Quantitative and Longitudinal Assessment of Preclinical Therapies

Published on: April 12, 2017

13.6K
Experimental Metastasis and CTL Adoptive Transfer Immunotherapy Mouse Model08:06

Experimental Metastasis and CTL Adoptive Transfer Immunotherapy Mouse Model

Published on: November 26, 2010

19.6K

Related Concept Videos

Adaptive Mechanisms in Cancer Cells02:53

Adaptive Mechanisms in Cancer Cells

Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
5.8K
Intracellular Signaling Affects Focal Adhesions01:17

Intracellular Signaling Affects Focal Adhesions

Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
2.7K
The Tumor Microenvironment02:17

The Tumor Microenvironment

Every normal cell or tissue is embedded in a complex local environment called stroma, consisting of different cell types, a basal membrane, and blood vessels. As normal cells mutate and develop into cancer cells, their local environment also changes to allow cancer progression. The tumor microenvironment (TME) consists of a complex cellular matrix of stromal cells and the developing tumor. The cross-talk between cancer cells and surrounding stromal cells is critical to disrupt normal tissue...
6.7K
Tumor Immunotherapy01:27

Tumor Immunotherapy

Immunotherapy is a treatment that boosts or manipulates the immune system to fight diseases, including cancer. For instance, by stimulating an immune response through vaccinations against viruses that cause cancers, like hepatitis B virus and human papillomavirus, these diseases can be prevented. Nonetheless, some cancer cells can avoid the immune system due to their rapid mutation and division. The immune response to many cancers involves three phases: elimination, equilibrium, and escape.
575
Treatment Resistant Cancers02:56

Treatment Resistant Cancers

Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
3.4K
Metastasis02:30

Metastasis

Metastasis is the spread of cancer cells from the original site to distant locations in the body. Cancer cells can spread via blood vessels (hematogenous) as well as lymph vessels in the body.
Epithelial-to-Mesenchymal Transition
The epithelial-to-mesenchymal transition or EMT is a developmental process commonly observed in wound healing, embryogenesis, and cancer metastasis. EMT is induced by transforming growth factor-beta (TGF-β) or receptor tyrosine kinase (RTK) ligands, which further...
5.6K