Mastl kinase, a promising therapeutic target, promotes cancer recurrence.
Mastl kinase promotes mitotic progression and cell cycle reentry after DNA damage. We report here that Mastl is frequently upregulated in various types of cancer. This upregulation was correlated with cancer progression in breast and oral cancer, poor patient survival in breast cancer, and tumor recurrence in head and neck squamous cell carcinoma. We further investigated the role of Mastl in tumor resistance using cell lines derived from the initial and recurrent tumors of the same head and neck squamous cell carcinoma patients. Ectopic expression of Mastl in the initial tumor cells strongly promoted cell proliferation in the presence of cisplatin by attenuating DNA damage signaling and cell death. Mastl knockdown in recurrent tumor cells re-sensitized their response to cancer therapy in vitro and in vivo. Finally, Mastl targeting specifically potentiated cancer cells to cell death in chemotherapy while sparing normal cells. Thus, this study revealed that Mastl upregulation is involved in cancer progression and tumor recurrence after initial cancer therapy, and validated Mastl as a promising target to increase the therapeutic window.
Department of Oral Biology, College of Dentistry, University of Nebraska Medical Center, Lincoln, NE 68583.
Ling
L
Wang
Department of Oral Biology, College of Dentistry, University of Nebraska Medical Center, Lincoln, NE 68583.
Vivian Q
VQ
Luong
Department of Oral Biology, College of Dentistry, University of Nebraska Medical Center, Lincoln, NE 68583.
Peter J
PJ
Giannini
Department of Oral Biology, College of Dentistry, University of Nebraska Medical Center, Lincoln, NE 68583.
Aimin
A
Peng
D000368:Aged; D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002945:Cisplatin / Q000737:chemistry; D004249:DNA Damage; D018450:Disease Progression; D000939:Epitopes / Q000737:chemistry; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000378:metabolism; D009364:Neoplasm Recurrence, Local / Q000378:metabolism*; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000473:pathology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D015398:Signal Transduction; D015854:Up-Regulation
D000939:Epitopes; D008869:Microtubule-Associated Proteins; C555237:MASTL protein, human; D017346:Protein Serine-Threonine Kinases; D002945:Cisplatin