Tumor Suppressor Protein p53 and Inhibitor of Apoptosis Proteins in Colorectal Cancer-A Promising Signaling Network for Therapeutic Interventions.
Ömer GüllülüStephanie HehlgansClaus RödelEmmanouil FokasFranz RödelPublished in: Cancers (2021)
Despite recent advances in the treatment of colorectal cancer (CRC), patient's individual response and clinical follow-up vary considerably with tumor intrinsic factors to contribute to an enhanced malignancy and therapy resistance. Among these markers, upregulation of members of the inhibitor of apoptosis protein (IAP) family effects on tumorigenesis and radiation- and chemo-resistance by multiple pathways, covering a hampered induction of apoptosis/autophagy, regulation of cell cycle progression and DNA damage response. These mechanisms are tightly controlled by the tumor suppressor p53 and thus transcriptional and post-translational regulation of IAPs by p53 is expected to occur in malignant cells. By this, cellular IAP1/2, X-linked IAP, Survivin, BRUCE and LIVIN expression/activity, as well as their intracellular localization is controlled by p53 in a direct or indirect manner via modulating a multitude of mechanisms. These cover, among others, transcriptional repression and the signal transducer and activator of transcription (STAT)3 pathway. In addition, p53 mutations contribute to deregulated IAP expression and resistance to therapy. This review aims at highlighting the mechanistic and clinical importance of IAP regulation by p53 in CRC and describing potential therapeutic strategies based on this interrelationship.
Keyphrases
- cell cycle arrest
- endoplasmic reticulum stress
- cell death
- cell cycle
- induced apoptosis
- poor prognosis
- oxidative stress
- cell proliferation
- dna damage response
- pi k akt
- signaling pathway
- binding protein
- transcription factor
- gene expression
- long non coding rna
- photodynamic therapy
- amino acid
- protein protein
- physical activity
- combination therapy
- stem cells
- case report
- nuclear factor
- risk assessment
- dna damage
- squamous cell carcinoma
- bone marrow
- cancer therapy
- inflammatory response
- climate change
- human health