Retinoic acid signaling and bladder cancer: Epigenetic deregulation, therapy and beyond

Ozgun G., ŞENTÜRK Ş., Erkek-Ozhan S.

INTERNATIONAL JOURNAL OF CANCER, cilt.148, sa.10, ss.2364-2374, 2021 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Derleme
  • Cilt numarası: 148 Sayı: 10
  • Basım Tarihi: 2021
  • Doi Numarası: 10.1002/ijc.33374
  • Dergi Adı: INTERNATIONAL JOURNAL OF CANCER
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, PASCAL, BIOSIS, Biotechnology Research Abstracts, CAB Abstracts, Chemical Abstracts Core, EMBASE, Food Science & Technology Abstracts, Gender Studies Database, MEDLINE, Veterinary Science Database
  • Sayfa Sayıları: ss.2364-2374
  • Anahtar Kelimeler: bladder cancer, epigenetic deregulation, retinoic acid, ABERRANT PROMOTER METHYLATION, ACTIVATED RECEPTOR-GAMMA, RENAL-CELL-CARCINOMA, VALPROIC ACID, PPAR-GAMMA, STEM-CELLS, TERMINAL DIFFERENTIATION, 13-CIS-RETINOIC ACID, SQUAMOUS METAPLASIA, INDUCED APOPTOSIS
  • Dokuz Eylül Üniversitesi Adresli: Evet

Özet

Retinoic acid (RA) signaling is a crucial developmental pathway involved in urothelium development, differentiation and regeneration. Deregulation of the RA signaling is highly implicated in several cancers, including bladder cancer, underlying the need to unravel the complete regulatory aspects of the retinoids in bladder tumorigenesis. Given the fact that RA receptors are transcription factors functioning at the chromatin level and act in close cooperation with chromatin modifiers, it is known that retinoids show their efficacy by changing the epigenome. Bladder cancer can be defined as a "disease of chromatin" with mutations identified in the genes involved in chromatin regulation in 80% of the patients. Therefore, a careful examination of the epigenetic backgrounds and the breakdown of the emerging and highly underexplored field of RA dependent regulation of the epigenome is essential to fully understand the retinoid-dependent effects on bladder cancer. With this motivation, in this review, we evaluate the role of RA signaling in bladder cancer with a focus on the regulatory and mutational aspects, emphasizing the deregulatory characteristics in bladder cancer and highlighting the potential treatment opportunities with the RA and derivatives alone or in combination with epigenetic drugs.