PFKFB4 Drives the Oncogenicity in TP53-Mutated Hepatocellular Carcinoma in a Phosphatase-Dependent Manner

Kam, Charles Shing; Ho, Daniel Chi Wing; Ming, Vanessa Sheung-In; Tian, Lü; Sze, Karen Man‐Fong; Zhang, Vanilla Xin; Tsui, Y; Husain, Abdullah; Lee, Joyce Man‐Fong; Wong, Carmen Chak‐Lui; Chan, Albert Chi‐Yan; Cheung, T.H.; Chan, Lap Ki; Ng, Irene Oi Lin

doi:10.1016/j.jcmgh.2023.02.004

Cited by 7 publications

(3 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…qRT-PCR was performed as described 48 , 49 , using ABI Power SYBR® Green master mix and detected by ABI QuantStudio 5 Real-Time PCR System (Applied Biosystems, Foster City, CA). The primer sequences are listed in supplementary Table S3 .…”

Section: Methodsmentioning

confidence: 99%

Reciprocal interactions between malignant cells and macrophages enhance cancer stemness and M2 polarization in HBV-associated hepatocellular carcinoma

Zhang,

Tsui,

Zhang

et al. 2024

Theranostics

View full text Add to dashboard Cite

Background:The tumor microenvironment of cancers has emerged as a crucial component in regulating cancer stemness and plays a pivotal role in cell-cell communication. However, the specific mechanisms underlying these phenomena remain poorly understood. Methods: We performed the single-cell RNA sequencing (scRNA-seq) on nine HBV-associated hepatocellular carcinoma (HCC) patients. The heterogeneity of the malignant cells in pathway functions, transcription factors (TFs) regulation, overall survival, stemness, as well as ligand-receptor-based intercellular communication with macrophages were characterized. The aggressive and stemness feature for the target tumor subclone was validated by the conduction of in vitro assays including sphere formation, proliferation, Annexin V apoptosis, flow cytometry, siRNA library screening assays, and multiple in vivo preclinical mouse models including mouse hepatoma cell and human HCC cell xenograft models with subcutaneous or orthotopic injection. Results: Our analysis yielded a comprehensive atlas of 31,664 cells, revealing a diverse array of malignant cell subpopulations. Notably, we identified a stemness-related subclone of HCC cells with concurrent upregulation of CD24, CD47, and ICAM1 expression that correlated with poorer overall survival. Functional characterization both in vitro and in vivo validated S100A11 as one of the top downstream mediators for tumor initiation and stemness maintenance of this subclone. Further investigation of cell-cell communication within the tumor microenvironment revealed a propensity for bi-directional crosstalk between this stemness-related subclone and tumor-associated macrophages (TAMs). Co-culture study showed that this interaction resulted in the maintenance of the expression of cancer stem cell markers and driving M2-like TAM polarization towards a pro-tumorigenic niche. We also consolidated an inverse relationship between the proportions of TAMs and tumor-infiltrating T cells. Conclusions: Our study highlighted the critical role of stemness-related cancer cell populations in driving an immunosuppressive tumor microenvironment and identified the S100A11 gene as a key mediator for stemness maintenance in HCC. Moreover, our study provides support that the maintenance of cancer stemness is more attributed to M2 polarization than the recruitment of the TAMs.

show abstract

Section: Methodsmentioning

confidence: 99%

Reciprocal interactions between malignant cells and macrophages enhance cancer stemness and M2 polarization in HBV-associated hepatocellular carcinoma

Zhang,

Tsui,

Zhang

et al. 2024

Theranostics

View full text Add to dashboard Cite

show abstract

“…KRAS mutation has been reported to directly regulate the enzymatic activity of hexokinase 1, thereby increasing glucose utilization by tumor cells ( 82 ). Overexpression of phosphofructokinases and pyruvate kinases in tumor tissues has also been confirmed to be involved in tumor growth and invasion ( 83 , 84 ). Several studies have consistently found that patients with cancer show relatively high levels of pyruvate in the blood and urine.…”

Section: Metabolomic Biomarkers For Cancer Screening and Diagnosismentioning

confidence: 99%

Metabolomic biomarkers in liquid biopsy: accurate cancer diagnosis and prognosis monitoring

Wang,

Zhen,

Ping

et al. 2024

Front. Oncol.

View full text Add to dashboard Cite

Liquid biopsy, a novel detection method, has recently become an active research area in clinical cancer owing to its unique advantages. Studies on circulating free DNA, circulating tumor cells, and exosomes obtained by liquid biopsy have shown great advances and they have entered clinical practice as new cancer biomarkers. The metabolism of the body is dynamic as cancer originates and progresses. Metabolic abnormalities caused by cancer can be detected in the blood, sputum, urine, and other biological fluids via systemic or local circulation. A considerable number of recent studies have focused on the roles of metabolic molecules in cancer. The purpose of this review is to provide an overview of metabolic markers from various biological fluids in the latest clinical studies, which may contribute to cancer screening and diagnosis, differentiation of cancer typing, grading and staging, and prediction of therapeutic response and prognosis.

show abstract

“…In this issue of Cellular and Molecular Gastroenterology and Hepatology , Kam et al 5 investigated the potential role of phosphofructokinase-fructose bisphosphatase 4 (PFKFB4), an activator of the key regulatory enzyme of glycolysis phosphofructokinase 1 (PFK1), in the pathogenesis of HCC. The investigators found that PFKFB4 expression was upregulated in HCC tumors from 3 independent cohorts of patients compared to non-malignant liver tissues, being associated with larger tumor size, advanced tumor stage or invasion, and reduced patient overall survival.…”

mentioning

confidence: 99%

PFKFB4 Is a Metabolic Driver of HCC Progression and Chemoresistance Through ROS Mitigation

Olaizola¹

2023

Cellular and Molecular Gastroenterology and Hepatology

View full text Add to dashboard Cite

PFKFB4 Drives the Oncogenicity in TP53-Mutated Hepatocellular Carcinoma in a Phosphatase-Dependent Manner

Cited by 7 publications

References 40 publications

Reciprocal interactions between malignant cells and macrophages enhance cancer stemness and M2 polarization in HBV-associated hepatocellular carcinoma

Reciprocal interactions between malignant cells and macrophages enhance cancer stemness and M2 polarization in HBV-associated hepatocellular carcinoma

Metabolomic biomarkers in liquid biopsy: accurate cancer diagnosis and prognosis monitoring

PFKFB4 Is a Metabolic Driver of HCC Progression and Chemoresistance Through ROS Mitigation

Contact Info

Product

Resources

About