Abstract
Colorectal cancer (CRC) poses a formidable challenge in terms of molecular heterogeneity, as it involves a variety of cancer-related pathways and molecular changes unique to an individual's tumor. On the other hand, recent advances in DNA sequencing technologies provide an unprecedented capacity to comprehensively identify the genetic alterations resulting in tumorigenesis, raising the hope that new therapeutic approaches based on molecularly targeted drugs may prevent the occurrence of chemoresistance. Regulation of the transcription factor FOXO3a in response to extracellular cues plays a fundamental role in cellular homeostasis, being part of the molecular machinery that drives cells towards survival or death. Indeed, FOXO3a is controlled by a range of external stimuli, which not only influence its transcriptional activity, but also affect its subcellular localization. These regulation mechanisms are mediated by cancer-related signaling pathways that eventually drive changes in FOXO3a post-translational modifications (e.g., phosphorylation). Recent results showed that FOXO3a is imported into the mitochondria in tumor cells and tissues subjected to metabolic stress and cancer therapeutics, where it induces expression of the mitochondrial genome to support mitochondrial metabolism and cell survival. The current review discusses the potential clinical relevance of multidrug therapies that drive cancer cell fate by regulating critical pathways converging on FOXO3a.
| Original language | English |
|---|---|
| Journal | Cancers |
| Volume | 11 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - Mar 23 2019 |
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Chasing the FOXO3 : Insights into Its New Mitochondrial Lair in Colorectal Cancer Landscape. / Grossi, Valentina; Fasano, Candida; Celestini, Valentina; Lepore Signorile, Martina; Sanese, Paola; Simone, Cristiano.
In: Cancers, Vol. 11, No. 3, 23.03.2019.Research output: Contribution to journal › Review article
}
TY - JOUR
T1 - Chasing the FOXO3
T2 - Insights into Its New Mitochondrial Lair in Colorectal Cancer Landscape
AU - Grossi, Valentina
AU - Fasano, Candida
AU - Celestini, Valentina
AU - Lepore Signorile, Martina
AU - Sanese, Paola
AU - Simone, Cristiano
PY - 2019/3/23
Y1 - 2019/3/23
N2 - Colorectal cancer (CRC) poses a formidable challenge in terms of molecular heterogeneity, as it involves a variety of cancer-related pathways and molecular changes unique to an individual's tumor. On the other hand, recent advances in DNA sequencing technologies provide an unprecedented capacity to comprehensively identify the genetic alterations resulting in tumorigenesis, raising the hope that new therapeutic approaches based on molecularly targeted drugs may prevent the occurrence of chemoresistance. Regulation of the transcription factor FOXO3a in response to extracellular cues plays a fundamental role in cellular homeostasis, being part of the molecular machinery that drives cells towards survival or death. Indeed, FOXO3a is controlled by a range of external stimuli, which not only influence its transcriptional activity, but also affect its subcellular localization. These regulation mechanisms are mediated by cancer-related signaling pathways that eventually drive changes in FOXO3a post-translational modifications (e.g., phosphorylation). Recent results showed that FOXO3a is imported into the mitochondria in tumor cells and tissues subjected to metabolic stress and cancer therapeutics, where it induces expression of the mitochondrial genome to support mitochondrial metabolism and cell survival. The current review discusses the potential clinical relevance of multidrug therapies that drive cancer cell fate by regulating critical pathways converging on FOXO3a.
AB - Colorectal cancer (CRC) poses a formidable challenge in terms of molecular heterogeneity, as it involves a variety of cancer-related pathways and molecular changes unique to an individual's tumor. On the other hand, recent advances in DNA sequencing technologies provide an unprecedented capacity to comprehensively identify the genetic alterations resulting in tumorigenesis, raising the hope that new therapeutic approaches based on molecularly targeted drugs may prevent the occurrence of chemoresistance. Regulation of the transcription factor FOXO3a in response to extracellular cues plays a fundamental role in cellular homeostasis, being part of the molecular machinery that drives cells towards survival or death. Indeed, FOXO3a is controlled by a range of external stimuli, which not only influence its transcriptional activity, but also affect its subcellular localization. These regulation mechanisms are mediated by cancer-related signaling pathways that eventually drive changes in FOXO3a post-translational modifications (e.g., phosphorylation). Recent results showed that FOXO3a is imported into the mitochondria in tumor cells and tissues subjected to metabolic stress and cancer therapeutics, where it induces expression of the mitochondrial genome to support mitochondrial metabolism and cell survival. The current review discusses the potential clinical relevance of multidrug therapies that drive cancer cell fate by regulating critical pathways converging on FOXO3a.
U2 - 10.3390/cancers11030414
DO - 10.3390/cancers11030414
M3 - Review article
C2 - 30909600
VL - 11
JO - Cancers
JF - Cancers
SN - 2072-6694
IS - 3
ER -