Role of eIF4A1 in triple‐negative breast cancer stem‐like cell‐mediated drug resistance

Abstract

In cap-dependent translation, the eukaryotic translation initiation factor 4A (eIF4A1) is an mRNA helicase is involved in unwinding of the secondary structure, such as the stem-loops, at the 5 0 -leader regions of the key oncogenic mRNAs. This facilitates ribosomal scanning and translation of the oncogenic mRNAs. eIF4A1 has a regulatory role in translating many oncoproteins that have vital roles in several steps of metastases. Sridharan et. al. have discovered and provide a novel insight into how eIF4A1 can play a regulatory role in drug resistance by influencing the levels of pluripotent Yamanaka transcription factors and ATP-binding cassette (ABC) transporters in triple-negative breast cancer (TNBC) stem-like cells. These findings may help us understand the molecular underpinnings of chemoresistance, especially in established metastases in TNBC. Importantly, eIF4A1 may form a novel clinical target in metastatic TNBC and the drug eFT226 from Effector Therapeutics targeting eIF4A1 is already in phase1-2 clinical trial.

Identification and Verification of m7G Modification Patterns and Characterization of Tumor Microenvironment Infiltration via Multi-Omics Analysis in Clear Cell Renal Cell Carcinoma

“…The level of EIF4A1 was also positively related to the ccRCC stage, which may reveal EIF4A1 as a hub gene in TME shaped by m 7 G modification. Several studies have reported the tumor−promoting effect of EIF4A1 in gastric cancer ( 86 ) and breast cancer ( 87 , 88 ) by promoting oncogene translation. Our findings offer an alternate explanation that EIF4A1 could regulate m 7 G modification and influence the immune infiltration landscape in the TME.…”

Emerging concepts in cancer therapy: Mechanisms of resistance

“…Besides, eIF4A1 also regulates the expression of drug transporters on tumor cell surface, thus contributing to chemoresistance. Hence, the authors emphasize the importance and potential of targeting eIF4A1 in preventing TNBC metastasis and reversing the resistance to therapy 16 …”

“…Tiwari have provided a commentary on the underlying mechanisms of metastasis and disease progression with special reference to cancer stem cells and their role in disease recurrence. 16 They identified the role of eukaryotic translation initiation factor 4A1 (eIF4A1) in cancer cell stemness and in regulating translation of oncoproteins such as survivin, cyclins, Rho kinase 1, and ADP ribosylation factor 6. These eIF4A1‐regulated proteins are vital for tumor cell survival, proliferation, migration, invasion, and chemoresistance.…”

“…Hence, the authors emphasize the importance and potential of targeting eIF4A1 in preventing TNBC metastasis and reversing the resistance to therapy. 16 …”