We investigate how cell-cycle control, neuro–tumor–immune signaling, and circadian disruption cooperate to drive cancer malignancy under psychological stress, and translate those mechanisms into targeted therapies.

Science

Research Areas

Circadian Disruption & Metabolism

Circadian Disruption & Metabolism

Sleep deficiency disrupts the circadian clock to fuel tumorigenesis through oncogenic metabolism. Circadian disruption dysregulates CLOCK, hyper-trans-activating ACSL1 to raise palmitoyl-CoA; ZDHHC5-mediated CLOCK-Cys194 S-palmitoylation then stabilizes CLOCK against proteasomal degradation, forming a transcription-palmitoylation feedback loop in which fatty-acid oxidation senses circadian disruption to drive cancer stemness. Timed beta-endorphin chronotherapy resets the CLOCK/ACSL1 rhythm and reverses sleep-deficiency-enhanced tumorigenesis.

Circadian ClockFatty-Acid OxidationCLOCK-ACSL1 LoopChronotherapy
Cell Metabolism, 2024
Mitotic Kinases Remodel the ER

Mitotic Kinases Remodel the ER

A mitotic kinase-Rab GTPase axis remodels the endoplasmic reticulum during cell division. During mitosis, Aurora kinase A (AURKA) phosphorylates the small GTPase Rab1A at Thr75, locking it in a constitutively active state by blocking GDI binding. ER-retained active Rab1A drives oligomerization of the ER-shaping proteins RTNs/REEPs, increasing ER complexity as cells progress from prometaphase to metaphase. This mechanism is evolutionarily conserved from C. elegans and Drosophila to mammals, revealing how mitotic signaling controls organelle architecture.

Aurora Kinase ARab1AER RemodelingMitosis
Nature Structural & Molecular Biology, 2023
Neural Signals & Cancer Stemness

Neural Signals & Cancer Stemness

Cancer cells hijack microenvironmental neural signals to acquire stemness. Norepinephrine released by sympathetic nerves activates the cAMP-CRE axis in proximal cancer cells, where ATF1 serves as a conserved hub. Activated ATF1 coordinately trans-activates nuclear pluripotency factors (MYC/NANOG) and mitochondrial-biogenesis regulators (NRF1/TFAM), orchestrating a nucleus-mitochondria collaborative program that establishes a spatialized hierarchy of cancer stemness. We target this neuro-tumor axis to disrupt stemness at its source.

NorepinephrinecAMP-CRE/ATF1Nucleus-MitochondriaCancer Stemness
Signal Transduction and Targeted Therapy, 2023
AURKA-m6A-DROSHA Axis

AURKA-m6A-DROSHA Axis

Oncogenic AURKA sustains breast cancer stem-like cells (BCSCs) by rewiring RNA epigenetic modification. AURKA stabilizes the m6A writer METTL14 and, together with the m6A reader IGF2BP2, enhances N6-methyladenosine (m6A) modification of DROSHA mRNA, increasing its stability. Stabilized DROSHA then complexes with beta-Catenin/TCF4 to trans-activate STC1 in an RNA-cleavage-independent manner, maintaining the stem-like state. Disrupting this AURKA-m6A-DROSHA axis attenuates BCSC traits, defining a targetable node in breast cancer stemness.

Aurora Kinase Am6A ModificationDROSHA-STC1BCSC Targeting
Cell Research, 2021
Recent Work

Selected Publications

2024
Oncogenic Fatty Acid Oxidation Senses Circadian Disruption in Sleep-Deficiency-Enhanced Tumorigenesis.
Peng F, Lu J, Su K, Liu X, Luo H, He B, Wang C, Zhang X, An F, Lv D, Luo Y, Su Q, Jiang T, Deng Z, He B, Xu L, Guo T, Xiang J, Gu C, Wang L, Xu G, Xu Y, Li M, Kelley K, Cui B, Liu Q
Cell Metabolism · 36(7): 1598–1618 · DOI: 10.1016/j.cmet.2024.04.018
2024
Aurora Kinase A-Mediated Phosphorylation Triggers Structural Alteration of Rab1A to Enhance ER Complexity during Mitosis.
Zhang W, Zhang Z, Xiang Y, Gu D, Chen J, Chen Y, Zhai S, Liu Y, Jiang T, Liu C, He B, Yan M, Wang Z, Xu J, Cao Y, Deng B, Zeng D, Lei J, Zhuo J, Lei X, Long Z, Jin B, Chen T, Li D, Shen Y, Hu J, Gao S, Liu Q
Nature Structural & Molecular Biology · 31(2): 219–231 · DOI: 10.1038/s41594-023-01165-7
2023
Cancer Cell Employs a Microenvironmental Neural Signal Trans-Activating Nucleus-Mitochondria Coordination to Acquire Stemness.
He B, Gao R, Lv S, Chen A, Huang J, Wang L, Feng Y, Feng J, Liu B, Lei J, Deng B, He B, Cui B, Peng F, Yan M, Wang Z, Lam E, Jin B, Shao Z, Li Y, Jiao J, Wang X, Liu Q
Signal Transduction and Targeted Therapy · 8(1): 275 · DOI: 10.1038/s41392-023-01487-4
2022
Nuclear Aurora Kinase A Switches m6A Reader YTHDC1 to Enhance an Oncogenic RNA Splicing of Tumor Suppressor RBM4.
Li S, Qi Y, Yu J, Hao Y, He B, Zhang M, Dai Z, Jiang T, Li S, Huang F, Chen N, Wang J, Yang M, Liang D, An F, Zhao J, Fan W, Pan Y, Deng Z, Luo Y, Guo T, Peng F, Hou Z, Wang C, Zheng F, Xu L, Xu J, Wen Q, Jin B, Wang Y, Liu Q
Signal Transduction and Targeted Therapy · 7(1): 97 · DOI: 10.1038/s41392-022-00905-3
2022
cGAS/STING cross-talks with cell cycle and potentiates cancer immunotherapy.
Long Z, Wang J, Xu J, Lei X, Liu Q
Molecular Therapy · 30(3): 1006–1017 · DOI: 10.1016/j.ymthe.2022.01.044
2022
A Temporal PROTAC Cocktail-mediated Sequential Degradation of AURKA Abrogates Acute Myeloid Leukemia Stem Cells.
Liu F, Wang X, Duan J, Hou Z, Wu Z, Liu L, Lei H, Huang D, Ren Y, Wang Y, Li X, Zhuo J, Zhang Z, He B, Yan M, Yuan H, Zhang L, Yan J, Wen S, Wang Z, Liu Q
Advanced Science · 9(22): 2104823 · DOI: 10.1002/advs.202104823
2021
Oncogenic AURKA-Enhanced N6-Methyladenosine Modification Increases DROSHA mRNA Stability to Transactivate STC1 in Breast Cancer Stem-like Cells.
Peng F, Xu J, Cui B, Liang Q, Zeng S, He B, Zou H, Li M, Zhao H, Meng Y, Chen J, Liu B, Lv S, Chu P, An F, Wang Z, Huang J, Zhan Y, Liao Y, Lu J, Xu L, Zhang J, Sun Z, Li Z, Wang F, Lam E, Liu Q
Cell Research · 31(3): 345–361 · DOI: 10.1038/s41422-020-00397-2
2021
Cancer and Stress: NextGen Strategies.
Cui B, Peng F, Lu J, He B, Su Q, Luo H, Deng Z, Jiang T, Su K, Huang Y, Ud Din Z, Lam E, Kelley K, Liu Q
Brain, Behavior, and Immunity · 93: 368–383 · DOI: 10.1016/j.bbi.2020.11.005
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Lab Life

Beyond the Bench

Teachers' Day Celebration
Teachers' Day Celebration
Lab Group Activity
Lab Group Activity
Lab Group Activity
Lab Group Activity
A Message from the Principal Investigator

Cancer remains one of the most formidable challenges in modern medicine. Our laboratory is driven by a fundamental question: how do cancer stem cells sustain themselves, resist therapy, and hijack the body's own stress responses to fuel malignant progression? We believe that curiosity, rigorous science, and fearless collaboration are the keys to answering these questions — and ultimately to developing cures. To every student and postdoc in this lab: I encourage you to think boldly, question everything, and never lose sight of the patients whose lives depend on what we discover.

Prof. Quentin Liu
Prof. Quentin Liu
Professor, Dalian Medical University