Two sides of the Myc-induced DNA damage response: from tumor suppression to tumor maintenance

Area of Science:

• Oncology
• Molecular Biology
• Cellular Signaling

Background:

• Oncogene activation, particularly of Myc, typically induces DNA damage response (DDR) signaling.
• DDR signaling acts as a critical barrier against tumor initiation and progression.
• Understanding the dual role of DDR in oncogenesis is crucial for developing targeted therapies.

Purpose of the Study:

• To review the multifaceted role of DNA damage response (DDR) signaling induced by oncogenic Myc.
• To elucidate the paradoxical functions of Myc-induced DDR in both tumor suppression and cancer cell survival.
• To highlight the distinct contributions of ATM/CHK2 and ATR/CHK1 pathways in these opposing roles.

Main Methods:

• This review synthesizes existing research on Myc-induced DDR.
• It focuses on the differential roles of ATM/CHK2 and ATR/CHK1 signaling branches.
• The analysis examines how these pathways influence tumor suppression and cancer cell viability.

Main Results:

• Myc activation induces DDR, which can suppress tumors via the ATM/CHK2 pathway.
• Conversely, Myc-induced replication stress is dampened by the ATR/CHK1 pathway, promoting cancer cell survival.
• These opposing DDR branches present a complex regulatory network in oncogenesis.

Conclusions:

• The Myc-induced DDR acts as a double-edged sword in tumor progression.
• ATM/CHK2 activation serves as a barrier to malignant transformation.
• ATR/CHK1 activation is vital for maintaining cancer cell viability, offering therapeutic targets.