Posts written by villelaj

PRC2-mediated epigenetic suppression of type I IFN-STAT2 signaling impairs antitumor immunity in luminal breast cancer

January 11, 2023

Abstract The immunosuppressive tumor microenvironment in some cancer types, such as luminal breast cancer, supports tumor growth and limits therapeutic efficacy. Identifying approaches to induce an immunostimulatory environment could help improve cancer treatment. Here, we demonstrate that inhibition of cancer-intrinsic EZH2 promotes antitumor immunity in estrogen receptor a-positive (ERa+) breast cancer. EZH2 is a component […]

HOTTIP Dependent R-loop Formation Regulates CTCF Boundary Activity and TAD Integrity in Leukemia

February 7, 2022

Abstract: HOTTIP lncRNA is highly expressed in acute myeloid leukemia (AML) patients carrying MLL rearrangement or NPM1 mutation to facilitate the formation of HOXA topologically associated domains (TADs) and drive aberrant transcription. However, the mechanism through which HOTTIP accesses CTCF chromatin boundaries and regulates CTCF-mediated genome topology remains unknown. Here, we show that HOTTIP directly […]

2-Hydroxyglutarate destabilizes chromatin regulatory landscape and lineage fidelity to promote cellular heterogeneity

January 27, 2022

Abstract: The epigenome delineates lineage-specific transcriptional programs and restricts cell plasticity to prevent non-physiological cell fate transitions. Although cell diversification fosters tumor evolution and therapy resistance, upstream mechanisms that regulate the stability and plasticity of the cancer epigenome remain elusive. Here we show that 2-hydroxyglutarate (2HG) not only suppresses DNA repair but also mediates the […]

Detecting cancer’s spread before it happens: research indicates it may be possible

October 25, 2021

Cancer that spreads, or metastasizes, to another area of the body is not typically as treatable as the primary tumor from which it originated. Survival from metastatic disease is generally poor. What if a daily or weekly blood sample could monitor each patient’s risk of metastasis, indicating the need for aggressive therapy before cancer spread […]

SNAI2-mediated repression of BIM protects rhabdomyosarcoma from ionizing radiation

September 13, 2021

Abstract Ionizing radiation (IR) and chemotherapy are mainstays of treatment for patients with rhabdomyosarcoma (RMS), yet the molecular mechanisms that underlie the success or failure of radiotherapy remain unclear. The transcriptional repressor SNAI2 was previously identified as a key regulator of IR sensitivity in normal and malignant stem cells through its repression of the proapoptotic […]

Regulation of telomere homeostasis and genomic stability in cancer by N6-adenosine methylation (m6A)

August 9, 2021

Abstract The role of RNA methylation on N6-adenosine (m6A) in cancer has been acknowledged, but the underlying mechanisms remain obscure. Here, we identified the homeobox containing 1 (HMBOX1) as an authentic target mRNA of m6A machinery, which is highly methylated in malignant cells compared to the normal counterparts and subject to expedited degradation upon the […]