Ferritin heavy chain (FTH1) exerts significant antigrowth effects in breast cancer cells by inhibiting the expression of c‐MYC

• Published in: FEBS open bio 2021-11, Vol.11 (11), p.3101-3114
• Main Authors: Ali, Amjad, Shafarin, Jasmin, Abu Jabal, Rola, Aljabi, Nour, Hamad, Mohamad, Sualeh Muhammad, Jibran, Unnikannan, Hema, Hamad, Mawieh
• Format: Article
• Language: English
• Subjects: Acids; Antibiotics; Antibodies; Apoferritins - biosynthesis; Apoptosis; Breast cancer; Breast Neoplasms - genetics; Breast Neoplasms - metabolism; Cancer therapies; Cell growth; Cell Line, Tumor; Cell Movement - genetics; Cell Proliferation - genetics; Chemotherapy; c‐MYC; Female; Ferritin; Ferritins - biosynthesis; Ferritins - genetics; Ferritins - metabolism; FTH1; G9a; Gene Expression - genetics; Gene Expression Regulation, Neoplastic - genetics; Humans; iron metabolism; Metabolism; Myc protein; Oxidoreductases - genetics; Oxidoreductases - metabolism; Penicillin; Proteins; Triple Negative Breast Neoplasms - genetics; Triple Negative Breast Neoplasms - metabolism; Tumor suppressor genes; Tumors
• ISSN: 2211-5463; 2211-5463
• DOI: 10.1002/2211-5463.13303

Overexpression of ferritin heavy chain (FTH1) often associates with good prognosis in breast cancer (BCa), particularly in the triple‐negative subtype (triple‐negative breast cancer). However, the mechanism by which FTH1 exerts its possible tumor suppressor effects in BCa is not known. Here, we examined the bearing of FTH1 silencing or overexpression on several aspects of BCa cell growth in vitro. FTH1 silencing promoted cell growth and mammosphere formation, increased c‐MYC expression, and reduced cell sensitivity to chemotherapy. In contrast, FTH1 overexpression inhibited cell growth, decreased c‐MYC expression, and sensitized cancer cells to chemotherapy; silencing of c‐MYC recapitulated the effects of FTH1 overexpression. These findings show for the first time that FTH1 suppresses tumor growth by inhibiting the expression of key oncogenes, such as c‐MYC. Similar to chemotherapy and iron chelation, increased expression of ferritin heavy chain 1 (FTH1) suppresses the expression of cellular myelocytomatosis and G9a in breast cancer (BCa) cells. This is associated with increased cellular iron influx, storage, and release and reduced BCa cell growth. These findings suggest that FTH1 acts as a tumor suppressor in BCa.