We show that these subtypes have differential sensitivity to clinical HER2/EGFR-targeted therapeutics, but small-molecule activators of PP2A, the phosphatase that regulates MYC Ser62 phosphorylation, circumvents these subtype-specific differences and ubiquitously suppresses tumor growth, demonstrating the therapeutic utility of this approach in targeting deregulated MYCbreast cancers.
In line with this notion, we found that PML is associated to the promoter regions of MYC and PIM1, consistent with their direct correlation in breast cancer specimens.
IMPLICATIONS: This study discovers a paradoxical role of c-MYC in promoting metastasis to the brain and in rendering brain-metastatic cells more susceptible to TRAIL, which suggests the existence of an Achilles' heel, thus providing a new therapeutic opportunity for breast cancer patients.
Finally, we demonstrate that TRA2β is regulated by the MYC oncogene, plays a role in metastasis maintenance in vivo, and its levels correlate with breast cancer patient survival.
We demonstrate the translational potential of an AMPK and BCL-2/BCL-X<sub>L</sub> co-targeting strategy in ex vivo and in vivo models of MYC-high breast cancer.
The enriched functional categories belonging to distinct combinatorial patterns are involved different oncogenic processes: cell proliferation (such as cell cycle control, estrogen responses, MYC and E2F targets) for mRNA expression in breast cancer, invasion and metastasis (such as cell adhesion and epithelial-mesenchymal transition (EMT)) for CNV in breast cancer, and diverse processes (such as immune and inflammatory responses, cell adhesion, angiogenesis, and EMT) for mRNA expression in GBM.
The expression of c-myc protein in breast cancer tissues was associated with plasma <i>C-MYC</i> level, even <i>C-MYC</i> level in supernatant of cancer cells was elevated.
Tumours with low ATM or high ATR levels in conjunction with MYC overexpression also have worse overall breast cancer-specific survival (BCSS) (p value < 0.05).
Gene network analyses suggested that MYC and TBX2 were the most significant upstream transcription factors in the breast cancers with high glucose uptake.
Emergence of resistance to hormonal interventions in estrogen-receptor (ER) positive BC coupled to loss of ER expression and activation of ER-independent growth factor, heat-shock, MYC and WNT pathways along with distinct mechanisms of therapeutic-resistance in HER2 over-expressing and triple-negative subtypes of BC collectively necessitates deeper profiling of the mechanistic networks regulated by potential lead anticancer compounds intended for further development to target BC.
The effect of MYC gene status on breast cancer patient outcome seems to depend on the underlying chromosomal instability and appears unfavorable for tumors with MYC amplification without polysomy.
This study supports the notion that MYC-driven tumor initiation relies on cell reprogramming, which is mediated by the activation of MYC-dependent oncogenic enhancers, thus establishing a therapeutic rational for treating basal-like breast cancers.
These findings suggest that a change in Shannon index for c-MYC CNV after neoadjuvant chemotherapy reflects chemo-responsiveness and that Shannon indices after neoadjuvant chemotherapy have a prognostic value in breast cancer patients who receive neoadjuvant chemotherapy.
The novel zinc finger protein 121 (ZNF121) has been demonstrated to physically and functionally associate with the MYC oncoprotein to regulate cell proliferation and likely breast cancer development.
Certain well-known oncogenes (MYC and HGF), cytokines (CSF2, IFNG and IL5) and microRNAs (miR-21, miR-155-5p and let-7) may participate in the ILF2 expression network in breast cancer.
We demonstrated that PRMT5 regulates OCT4/A, KLF4, and C-MYC in breast cancer to govern stemness and affects the doxorubicin resistance of breast cancer.