CDKN1A/p21 in Breast Cancer: Part of the Problem, or Part of the Solution?
Evangelos ManousakisClàudia Martinez MirallesMaria Guimerà EsquerdaRoni H G WrightPublished in: International journal of molecular sciences (2023)
Cyclin-dependent kinase inhibitor 1A (Cip1/Waf1/CDKN1A/p21) is a well-established protein, primarily recognised for its pivotal role in the cell cycle, where it induces cell cycle arrest by inhibiting the activity of cyclin-dependent kinases (CDKs). Over the years, extensive research has shed light on various additional mechanisms involving CDKN1A/p21, implicating it in processes such as apoptosis, DNA damage response (DDR), and the regulation of stem cell fate. Interestingly, p21 can function either as an oncogene or as a tumour suppressor in these contexts. Complicating matters further, the expression of CDKN1A/p21 is elevated in certain tumour types while downregulated in others. In this comprehensive review, we provide an overview of the multifaceted functions of CDKN1A/p21, present clinical data pertaining to cancer patients, and delve into potential strategies for targeting CDKN1A/p21 as a therapeutic approach to cancer. Manipulating CDKN1A/p21 shows great promise for therapy given its involvement in multiple cancer hallmarks, such as sustained cell proliferation, the renewal of cancer stem cells (CSCs), epithelial-mesenchymal transition (EMT), cell migration, and resistance to chemotherapy. Given the dual role of CDKN1A/p21 in these processes, a more in-depth understanding of its specific mechanisms of action and its regulatory network is imperative to establishing successful therapeutic interventions.
Keyphrases
- cell cycle
- cell cycle arrest
- cell proliferation
- epithelial mesenchymal transition
- cell death
- cancer stem cells
- cell migration
- dna damage response
- papillary thyroid
- pi k akt
- cell fate
- squamous cell
- oxidative stress
- physical activity
- optical coherence tomography
- stem cells
- big data
- squamous cell carcinoma
- transforming growth factor
- mesenchymal stem cells
- binding protein
- artificial intelligence
- long non coding rna
- lymph node metastasis
- network analysis
- replacement therapy
- cell therapy