Abnormal Expression of c-Myc Oncogene in NK Cells in Patients with Cancer

Abstract

Natural killer (NK) cells have received a lot of attention in recent years for the roles they play in immunity and particularly in antitumor immune responses. Although defects in NK cell functions are recognized as important mechanisms for immune evasion of malignant cells, molecular pathways regulating NK cell dysfunction and exhaustion in cancer are largely unknown. Here we tested whether the c-myc proto-oncogene, known to promote cell proliferation, growth, differentiation, and apoptosis by regulating the expression of numerous target genes, may be involved in the mechanism of NK cell abnormalities in patients with lung and gastric cancer. Analysis of c-myc mRNA and protein expression in peripheral blood NK cells, mitogen-activated protein kinase (MAPK) activity, cell cycle, and cell longevity revealed a significantly decreased expression of c-myc mRNA and protein and mitotic arrest of NK cells in different phases of cell cycle. In addition, a significant decrease of NK cell death was also detected. These data allow the suggestion that defects of NK cell-mediated tumor surveillance may be associated with disturbed c-myc expression in NK cells in cancer patients. A better understanding of the mechanisms of NK cell dysfunction in cancer will help in the NK cell-mediated therapeutic eradication of primary and metastatic cancer cells and prolong patient survival.

Establishing immune scoring model based on combination of the number, function, and phenotype of lymphocytes

“…These data suggest that innate immunity is more important for children and elders, because the function of adaptive immune cells is immature in children and the number of them is insufficient in elders. These data are consistent with previous findings indicating that NK cells play an important role in the immunity of elders and may be interpreted as a factor of longevity [20][21][22][23]. Many surface molecules are selectively expressed on different lymphocyte subsets and are described as lymphocyte phenotype.…”

Demethylzeylasteral inhibits proliferation, migration, and invasion through FBXW7/c‐Myc axis in gastric cancer

“…The proto‐oncogene c‐Myc encodes the transcription factor c‐Myc, which has been reported to bind to 15% of the promoters of whole human genome 12 . The c‐Myc expression and activity are strictly regulated due to its crucial roles in diverse cellular processes, such as cell differentiation, cell cycle progression, migration, invasion, and apoptosis involved in tumorigenesis and development 13–16 . c‐Myc is often overexpressed or over‐activated in many cancers, which is associated with the occurrence and development of various tumors 13 .…”

“… 12 The c‐Myc expression and activity are strictly regulated due to its crucial roles in diverse cellular processes, such as cell differentiation, cell cycle progression, migration, invasion, and apoptosis involved in tumorigenesis and development. 13 , 14 , 15 , 16 c‐Myc is often overexpressed or over‐activated in many cancers, which is associated with the occurrence and development of various tumors. 13 In most human tumor, its high expression and multiple downstream oncogenic pathways are often correlated with poor prognosis.…”

The new role for an old guy: MYC as an immunoplayer

“…Interestingly, impaired innate immune response against cancer cells is in correlation with reduced levels of MYC expression in NK cells. MYC messenger RNA and protein levels are significantly lower in peripheral and cancer‐infiltrating NK cells in patients with lung and gastric cancer (Zakiryanova et al, 2019). Downmodulation of MYC in NK cells is not induced by the activity of cancer cells, but rather it represents an inheritable defect that precedes cancer development (Zakiryanova et al, 2019).…”

“…MYC messenger RNA and protein levels are significantly lower in peripheral and cancer‐infiltrating NK cells in patients with lung and gastric cancer (Zakiryanova et al, 2019). Downmodulation of MYC in NK cells is not induced by the activity of cancer cells, but rather it represents an inheritable defect that precedes cancer development (Zakiryanova et al, 2019). The role of MYC in antitumor activity of NK cells is not restricted to their proliferation.…”