Scholars@Duke
Ling Cai

Ling Cai

Assistant Professor of Pathology
Pathology
ling.cai@duke.edu
905 S LaSalle St, GSRB1, Rm 2077, Durham, NC 27710

Selected Publications

The sotos syndrome gene Nsd1 safeguards developmental gene enhancers poised for transcription by maintaining the precise deposition of histone methylation.

Journal Article J Biol Chem · May 2025 Germline haploinsufficiency of NSD1 is implicated as the etiology of Sotos syndrome; however, the underlying mechanism remains far from being clear. Here, we use mouse embryonic stem cell (mESC) differentiation as a model system to address this question. W ... Full text Link to item Cite

The phenylalanine-and-glycine repeats of NUP98 oncofusions form condensates that selectively partition transcriptional coactivators.

Journal Article Mol Cell · February 20, 2025 Recurrent cancer-causing fusions of NUP98 produce higher-order assemblies known as condensates. How NUP98 oncofusion-driven condensates activate oncogenes remains poorly understood. Here, we investigate NUP98-PHF23, a leukemogenic chimera of the disordered ... Full text Link to item Cite

EZH2 PROTACs target EZH2- and FOXM1-associated oncogenic nodes, suppressing breast cancer cell growth.

Journal Article Oncogene · August 2024 Breast cancer (BC) remains the second leading cause of cancer-related mortalities in women. Resistance to hormone therapies such as tamoxifen, an estrogen receptor (ER) inhibitor, is a major hurdle in the treatment of BC. Enhancer of zeste homolog 2 (EZH2) ... Full text Link to item Cite

Through the lens of phase separation: intrinsically unstructured protein and chromatin looping.

Journal Article Nucleus · December 2023 The establishment, maintenance and dynamic regulation of three-dimensional (3D) chromatin structures provide an important means for partitioning of genome into functionally distinctive domains, which helps to define specialized gene expression programs ass ... Full text Open Access Link to item Cite

Dissecting and targeting noncanonical functions of EZH2 in multiple myeloma via an EZH2 degrader.

Journal Article Oncogene · March 2023 Multiple myeloma (MM) is the second most common hematological malignancy with poor prognosis. Enhancer of zeste homolog 2 (EZH2) is the enzymatic subunit of polycomb repressive complex 2 (PRC2), which catalyzes trimethylation of histone H3 lysine 27 (H3K27 ... Full text Link to item Cite

Epigenetic (De)regulation in Prostate Cancer.

Journal Article Cancer Treat Res · 2023 Prostate cancer (PCa) is a heterogeneous disease exhibiting both genetic and epigenetic deregulations. Epigenetic alterations are defined as changes not based on DNA sequence, which include those of DNA methylation, histone modification, and chromatin remo ... Full text Link to item Cite

A cryptic transactivation domain of EZH2 binds AR and AR's splice variant, promoting oncogene activation and tumorous transformation.

Journal Article Nucleic Acids Res · October 28, 2022 Enhancer of Zeste Homolog 2 (EZH2) and androgen receptor (AR) are crucial chromatin/gene regulators involved in the development and/or progression of prostate cancer, including advanced castration-resistant prostate cancer (CRPC). To sustain prostate tumor ... Full text Open Access Link to item Cite

Discovery of a dual WDR5 and Ikaros PROTAC degrader as an anti-cancer therapeutic.

Journal Article Oncogene · June 2022 WD repeat domain 5 (WDR5), an integral component of the MLL/KMT2A lysine methyltransferase complex, is critically involved in oncogenesis and represents an attractive onco-target. Inhibitors targeting protein-protein interactions (PPIs) between WDR5 and it ... Full text Link to item Cite

A PRC2-Kdm5b axis sustains tumorigenicity of acute myeloid leukemia.

Journal Article Proc Natl Acad Sci U S A · March 1, 2022 Acute myeloid leukemias (AMLs) with the NUP98-NSD1 or mixed lineage leukemia (MLL) rearrangement (MLL-r) share transcriptomic profiles associated with stemness-related gene signatures and display poor prognosis. The molecular underpinnings of AML aggressiv ... Full text Link to item Cite

EZH2 noncanonically binds cMyc and p300 through a cryptic transactivation domain to mediate gene activation and promote oncogenesis.

Journal Article Nat Cell Biol · March 2022 Canonically, EZH2 serves as the catalytic subunit of PRC2, which mediates H3K27me3 deposition and transcriptional repression. Here, we report that in acute leukaemias, EZH2 has additional noncanonical functions by binding cMyc at non-PRC2 targets and uses ... Full text Link to item Cite

Phase separation drives aberrant chromatin looping and cancer development.

Journal Article Nature · July 2021 The development of cancer is intimately associated with genetic abnormalities that target proteins with intrinsically disordered regions (IDRs). In human haematological malignancies, recurrent chromosomal translocation of nucleoporin (NUP98 or NUP214) gene ... Full text Link to item Cite

Cistrome analysis of YY1 uncovers a regulatory axis of YY1:BRD2/4-PFKP during tumorigenesis of advanced prostate cancer.

Journal Article Nucleic Acids Res · May 21, 2021 Castration-resistant prostate cancer (CRPC) is a terminal disease and the molecular underpinnings of CRPC development need to be better understood in order to improve its treatment. Here, we report that a transcription factor Yin Yang 1 (YY1) is significan ... Full text Open Access Link to item Cite

BAHCC1 binds H3K27me3 via a conserved BAH module to mediate gene silencing and oncogenesis.

Journal Article Nat Genet · December 2020 Trimethylated histone H3 lysine 27 (H3K27me3) regulates gene repression, cell-fate determination and differentiation. We report that a conserved bromo-adjacent homology (BAH) module of BAHCC1 (BAHCC1BAH) 'recognizes' H3K27me3 specifically and enforces sile ... Full text Link to item Cite

ZFX Mediates Non-canonical Oncogenic Functions of the Androgen Receptor Splice Variant 7 in Castrate-Resistant Prostate Cancer.

Journal Article Mol Cell · October 18, 2018 Androgen receptor splice variant 7 (AR-V7) is crucial for prostate cancer progression and therapeutic resistance. We show that, independent of ligand, AR-V7 binds both androgen-responsive elements (AREs) and non-canonical sites distinct from full-length AR ... Full text Open Access Link to item Cite

Glucocorticoid receptor confers resistance to antiandrogens by bypassing androgen receptor blockade.

Journal Article Cell · December 5, 2013 The treatment of advanced prostate cancer has been transformed by novel antiandrogen therapies such as enzalutamide. Here, we identify induction of glucocorticoid receptor (GR) expression as a common feature of drug-resistant tumors in a credentialed precl ... Full text Link to item Cite

Androgen receptor signaling regulates DNA repair in prostate cancers.

Journal Article Cancer Discov · November 2013 UNLABELLED: We demonstrate that the androgen receptor (AR) regulates a transcriptional program of DNA repair genes that promotes prostate cancer radioresistance, providing a potential mechanism by which androgen deprivation therapy synergizes with ionizing ... Full text Link to item Cite

An H3K36 methylation-engaging Tudor motif of polycomb-like proteins mediates PRC2 complex targeting.

Journal Article Mol Cell · February 7, 2013 Polycomb repressive complex 2 (PRC2) regulates pluripotency, differentiation, and tumorigenesis through catalysis of histone H3 lysine 27 trimethylation (H3K27me3) on chromatin. However, the mechanisms that underlie PRC2 recruitment and spreading on chroma ... Full text Link to item Cite

ARN-509: a novel antiandrogen for prostate cancer treatment.

Journal Article Cancer Res · March 15, 2012 Continued reliance on the androgen receptor (AR) is now understood as a core mechanism in castration-resistant prostate cancer (CRPC), the most advanced form of this disease. While established and novel AR pathway-targeting agents display clinical efficacy ... Full text Link to item Cite

NUP98-NSD1 links H3K36 methylation to Hox-A gene activation and leukaemogenesis.

Journal Article Nat Cell Biol · July 2007 Nuclear receptor-binding SET domain protein 1 (NSD1) prototype is a family of mammalian histone methyltransferases (NSD1, NSD2/MMSET/WHSC1, NSD3/WHSC1L1) that are essential in development and are mutated in human acute myeloid leukemia (AML), overgrowth sy ... Full text Link to item Cite

Opposing LSD1 complexes function in developmental gene activation and repression programmes.

Journal Article Nature · April 19, 2007 Precise control of transcriptional programmes underlying metazoan development is modulated by enzymatically active co-regulatory complexes, coupled with epigenetic strategies. One thing that remains unclear is how specific members of histone modification e ... Full text Link to item Cite

Transcriptional regulation of a metastasis suppressor gene by Tip60 and beta-catenin complexes.

Journal Article Nature · April 14, 2005 Defining the molecular strategies that integrate diverse signalling pathways in the expression of specific gene programmes that are critical in homeostasis and disease remains a central issue in biology. This is particularly pertinent in cancer biology bec ... Full text Link to item Cite