Fanconi anemia pathway regulation by FANCI in prostate cancer

Heidi Kaljunen1, Sinja Taavitsainen2, Roosa Kaarijärvi1

  • 1Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland.

Frontiers in Oncology
|November 29, 2023
PubMed

Insights

FANCI is crucial for prostate cancer cell survival and resistance to chemotherapy. Its inactivation may make cancer cells eradicable, offering new therapeutic strategies for this disease.

Area of Science:

  • Oncology
  • Cancer Genetics
  • Molecular Biology

Background:

  • Prostate cancer is a leading cause of male mortality worldwide.
  • Treatment resistance in prostate cancer necessitates research into underlying genetic factors.
  • The Fanconi anemia (FA) pathway plays a role in DNA repair and maintaining genomic stability.

Purpose of the Study:

  • To investigate the role of FANCI and the FA pathway in prostate cancer treatment resistance.
  • To determine if FANCI inactivation can sensitize prostate cancer cells to chemotherapy.
  • To assess the prevalence and prognostic significance of FA pathway alterations in prostate cancer patients.

Main Methods:

  • Utilized prostate cancer cell lines to study the effects of FANCI depletion.
  • Assessed proliferation and FA pathway member expression following FANCI silencing.
  • Analyzed genomic alteration data (mutations, copy number) for FA pathway genes in patient cohorts.

Main Results:

  • FANCI depletion significantly downregulated FA pathway members in prostate cancer cells.
  • FANCI silencing reduced proliferation in p53-expressing prostate cancer cells, suggesting a shift towards chemosensitivity.
  • High expression of FA pathway genes correlated with poorer patient survival.
  • Genomic alterations in FA pathway genes were prevalent, found in 59.2% of analyzed prostate adenocarcinoma samples.

Conclusions:

  • FANCI is a key regulator of the FA pathway in prostate cancer.
  • Inactivating FANCI may convert resistant cancer cells into a state susceptible to DNA-damaging chemotherapy.
  • Alterations in the FA pathway are common in prostate cancer and associated with adverse outcomes, highlighting its potential as a therapeutic target.

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...
4.5K
The Retinoblastoma Gene01:20

The Retinoblastoma Gene

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
4.1K
Canonical Wnt Signaling Pathway02:54

Canonical Wnt Signaling Pathway

The gene encoding the main signaling molecules of the Wnt signaling pathways (the Wnt proteins) was discovered almost four decades ago by Nüsslein-Volhard and Wieschaus. They identified and originally named the gene "wingless" (wg) after a phenotype discovered during their landmark genetic screen in Drosophila for body pattern defects. At around the same time, another researcher named Harold Varmus found that a murine tumor virus activates the mammalian wg homolog, Int-1, which...
8.8K
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
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...
6.3K
Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
2.6K