MYC dysfunction modulates stemness and tumorigenesis in breast cancer

Abstract

As a transcription factor and proto-oncogene, MYC is known to be deregulated in a variety of tumors, including breast cancer. However, no consistent conclusion on the role and mechanism of MYC deregulation during breast cancer carcinogenesis has been formed. Here, we used the UALCAN, bc-GenExMiner, TCGA, cBioportal, STRING and Kaplan-Meier Plotter databases to explore the mRNA expression, prognosis, transcriptional profile changes, signal pathway rewiring and interaction with the cancer stem cells of MYC in breast cancer. We found that the expression of MYC varies in different subtypes of breast cancer, with relatively high frequency in TNBC. As a transcription factor, MYC not only participates in the rewiring of cancer signaling pathways, such as estrogen, WNT, NOTCH and other pathways, but also interacts with cancer stem cells. MYC is significantly positively correlated with breast cancer stem cell markers such as CD44, CD24, and ALDH1. Collectively, our results highlight that MYC plays an important regulatory role in the occurrence of breast cancer, and its amplification can be used as a predictor of diagnosis and prognosis. The interaction between MYC and cancer stem cells may play a crucial role in regulating the initiation and metastasis of breast cancer.

Polyploid giant cancer cells, EZH2 and Myc upregulation in mammary epithelial cells infected with high-risk human cytomegalovirus

“… 56 Further, bromodomain-4 protein (BRD4) was shown to positively regulate EZH2 transcription through Myc upregulation. 57 Intriguingly, Myc activation was widely reported in breast cancer progression, particularly in triple-negative breast cancer and in tumors displaying drug resistant phenotype, 11 , 47 , 58 similarly to aggressive medulloblastoma tumors where higher Myc levels were associated with increased EZH2 expression. 59 On the other hand, by uncoupling DNA replication from mitosis, Myc overexpression can induce DNA replication, thus opening the door toward polyploidy.…”

“…On the other hand, polyploid giant cancer cells (PGCCs) are recognized as a cancerous cellular subpopulation endowed with an enhanced tumorigenic properties, tumor maintenance and recurrence, as well as therapy resistance, the latter accentuated by tumor heterogeneity. 9 , 10 , 11 Giant cancerous cells were described in a wide range of high-grade cancers, chemoresistant tumors and cancer cell lines, for instance glioma, breast, lung, prostate and colorectal cancer. 12 Being greatly dedifferentiated with embryonic stem-like traits, PGCCs are able to replicate through an asymmetric division pattern, resulting in the establishment of a mitotically-competent progeny population.…”

MYCL promotes the progression of triple‑negative breast cancer by activating the JAK/STAT3 pathway

“…A number of molecular markers have been demonstrated to regulate different types of cellular processes in TNBC (32). The MYC gene is a common intracellular proto-oncogene, which is highly expressed in a variety of tumors, including BC (16). Kato et al (15) reported that MYCL was highly expressed in SCLC cell lines.…”

“…Previous studies have also revealed that MYC expression is dysregulated in 30-50% of cases of high-grade BC. Compared with in normal breast tissues, MYC expression in tumor tissues has been shown to be decreased, and among the major subclasses, MYC expression is relatively high in TNBC (16). Compared with C-MYC or N-MYC, which drive several types of human cancer (17)(18)(19)(20), there are fewer studies on MYCL.…”

Identification of potential microRNA diagnostic panels and uncovering regulatory mechanisms in breast cancer pathogenesis

“…The BC- related TFs with the largest degree value were MYC, STAT3, NFKB1, RELA and SP1, respectively. A recent study demonstrated that MYC interacts with cancer stem cells and thus exerts an important role in regulating the initiation of BC, suggesting it may serve as a predictor of BC diagnosis 85 . Interestingly, plasma c-MYC level was reported to be significantly up-regulated in patients with primary BC compared to healthy controls, and that its high expression could be a potential indicator of BC progression 86 .…”