Targeting the glutamine-arginine-proline metabolism axis in cancer.

Metabolic abnormalities are an important feature of tumours. The glutamine-arginine-proline axis is an important node of cancer metabolism and plays a major role in amino acid metabolism. This axis also acts as a scaffold for the synthesis of other nonessential amino acids and essential metabolites.

Spindle apparatus coiled-coil protein 1 (SPDL1) serves as a novel prognostic biomarker in triple-negative breast cancer.

Background: Triple-negative breast cancer (TNBC) has a poor prognosis, an ineffective diagnosis, and a high degree of aggressiveness. Therefore, novel therapeutic targets for TNBC urgently need to be identified.

Methods: Through a series of bioinformatics analyses, including analysis of differential gene expression, protein-protein interaction (PPI) network, univariate cox regression, immune infiltration, pathway enrichment, etc, as well as auxiliary immunohistochemistry (IHC) and protein quantitativae analysis, to explore prognostic marker for TNBC.

Glioma-associated mesenchymal stem cells.

Recent studies have revealed that glioma-associated mesenchymal stem cells play instrumental roles in tumorigenesis and tumour progression and cannot be ignored as a cellular component of the glioma microenvironment. Nevertheless, the origin of these cells and their roles are poorly understood. The only relevant studies have shown that glioma-associated mesenchymal stem cells play a large role in promoting tumour proliferation, invasion and angiogenesis.

Mitochondria in cancer stem cells: Achilles heel or hard armor.

Previous studies have shown that mitochondria play core roles in not only cancer stem cell (CSC) metabolism but also the regulation of CSC stemness maintenance and differentiation, which are key regulators of cancer progression and therapeutic resistance. Therefore, an in-depth study of the regulatory mechanism of mitochondria in CSCs is expected to provide a new target for cancer therapy. This article mainly introduces the roles played by mitochondria and related mechanisms in CSC stemness maintenance, metabolic transformation, and chemoresistance.

Beyond metabolic waste: lysine lactylation and its potential roles in cancer progression and cell fate determination.

Background: Lactate is an important metabolite derived from glycolysis under physiological and pathological conditions. The Warburg effect reveals the vital role of lactate in cancer progression. Numerous studies have reported crucial roles for lactate in cancer progression and cell fate determination.

ALDEFLUOR activity, ALDH isoforms, and their clinical significance in cancers.

High aldehyde dehydrogenase (ALDH) activity is a metabolic feature of adult stem cells and various cancer stem cells (CSCs). The ALDEFLUOR system is currently the most commonly used method for evaluating ALDH enzyme activity in viable cells. This system is applied extensively in the isolation of normal stem cells and CSCs from heterogeneous cell populations.

Construction of a solid Cox model for AML patients based on multiomics bioinformatic analysis.

Acute myeloid leukemia (AML) is a highly heterogeneous hematological malignancy. The bone marrow (BM) microenvironment in AML plays an important role in leukemogenesis, drug resistance and leukemia relapse. In this study, we aimed to identify reliable immune-related biomarkers for AML prognosis by multiomics analysis.

ASCL2 Maintains Stemness Phenotype through ATG9B and Sensitizes Gliomas to Autophagy Inhibitor.

Autophagy is a highly conserved process that is vital for tumor progression and treatment response. Although autophagy is proposed to maintain the stemness phenotype in adult diffuse glioma, the molecular basis of the link between autophagy and stemness is poorly understood, which makes it impossible to effectively screen for the population that will benefit from autophagy-targeted treatment. Here, ATG9B as essential for self-renewal capacity and tumor-propagation potential is identified.

CRIPTO Is a Marker of Chemotherapy-Induced Stem Cell Expansion in Non-Small Cell Lung Cancer.

Chemotherapy is the mainstay for the treatment of non-small cell lung cancer (NSCLC). However, NSCLC cells are either intrinsically chemoresistant or rapidly develop therapy resistance. Cancer stem cells (CSCs) are widely recognized as the cell population responsible for resistance to systemic therapies, but the molecular responses of CSCs to chemotherapeutic agents are largely unknown.

An aldehyde dehydrogenase 1A3 inhibitor attenuates the metastasis of human colorectal cancer.

Metastasis is the leading cause of death for patients with colorectal cancer (CRC). The development of therapeutic regimens that selectively inhibit the biological processes involved in CRC cell dissemination is important. We used multiple Affymetrix DNA microarray hybridization datasets to identify genes related to metastasis and have significant prognostic value for patients with CRC.

Glioma invasion along white matter tracts: A dilemma for neurosurgeons.

Invasive growth along white matter (WM) tracts is one of the most prominent clinicopathological features of glioma and is also an important reason for surgical treatment failure in glioma patients. A full understanding of relevant clinical features and mechanisms is of great significance for finding new therapeutic targets and developing new treatment regimens and strategies. Herein, we review the imaging and histological characteristics of glioma patients with WM tracts invasion and summarize the possible molecular mechanism.

The role of lysosomes in cancer development and progression.

Lysosomes are an important component of the inner membrane system and participate in numerous cell biological processes, such as macromolecular degradation, antigen presentation, intracellular pathogen destruction, plasma membrane repair, exosome release, cell adhesion/migration and apoptosis. Thus, lysosomes play important roles in cellular activity. In addition, previous studies have shown that lysosomes may play important roles in cancer development and progression through the abovementioned biological processes and that the functional status and spatial distribution of lysosomes are closely related to cancer cell proliferation, energy metabolism, invasion and metastasis, immune escape and tumor-associated angiogenesis.

NADP modulates RNA mA methylation and adipogenesis via enhancing FTO activity.

Metabolism is often regulated by the transcription and translation of RNA. In turn, it is likely that some metabolites regulate enzymes controlling reversible RNA modification, such as N-methyladenosine (mA), to modulate RNA. This hypothesis is at least partially supported by the findings that multiple metabolic diseases are highly associated with fat mass and obesity-associated protein (FTO), an mA demethylase.

Triple-negative breast cancer molecular subtyping and treatment progress.

Triple-negative breast cancer (TNBC), a specific subtype of breast cancer that does not express estrogen receptor (ER), progesterone receptor (PR), or human epidermal growth factor receptor 2 (HER-2), has clinical features that include high invasiveness, high metastatic potential, proneness to relapse, and poor prognosis. Because TNBC tumors lack ER, PR, and HER2 expression, they are not sensitive to endocrine therapy or HER2 treatment, and standardized TNBC treatment regimens are still lacking. Therefore, development of new TNBC treatment strategies has become an urgent clinical need.

Icaritin enhances the efficacy of cetuximab against triple-negative breast cancer cells.

Triple-negative breast cancer (TNBC) has a greater risk of recurrence and metastasis along with a worse prognosis compared with other subtypes of breast cancer. Studies have revealed that mitogenic estrogen signaling is involved in the malignant proliferation of TNBC cells through a novel variant of the estrogen receptor, estrogen receptor α-36 (ER-α36). The results of the present study demonstrated that knockdown of ER-α36 expression in TNBC cells using short hairpin RNA inhibited rapid estrogen signaling bypass activation of the PI3K/AKT signaling pathway.

Inhibition of the ALDH18A1-MYCN positive feedback loop attenuates -amplified neuroblastoma growth.

-amplified neuroblastoma (NB) is characterized by poor prognosis, and directly targeting MYCN has proven challenging. Here, we showed that aldehyde dehydrogenase family 18 member A1 (ALDH18A1) exerts profound impacts on the proliferation, self-renewal, and tumorigenicity of NB cells and is a potential risk factor in patients with NB, especially those with amplification. Mechanistic studies revealed that ALDH18A1 could both transcriptionally and posttranscriptionally regulate MYCN expression, with MYCN reciprocally transactivating ALDH18A1 and thus forming a positive feedback loop.

CCL8 secreted by tumor-associated macrophages promotes invasion and stemness of glioblastoma cells via ERK1/2 signaling.

Tumor-associated macrophages (TAMs) constitute a large population of glioblastoma and facilitate tumor growth and invasion of tumor cells, but the underlying mechanism remains undefined. In this study, we demonstrate that chemokine (C-C motif) ligand 8 (CCL8) is highly expressed by TAMs and contributes to pseudopodia formation by GBM cells. The presence of CCL8 in the glioma microenvironment promotes progression of tumor cells.

Serum sPD-1 and sPD-L1 as Biomarkers for Evaluating the Efficacy of Neoadjuvant Chemotherapy in Triple-Negative Breast Cancer Patients.

Background: Neoadjuvant chemotherapy (NAC) is widely administered in the primary treatment of triple-negative breast cancer (TNBC). However, serum biomarkers for evaluating or monitoring the curative efficacy of NAC have not been established. Accumulating data have shown that soluble programmed death 1 (sPD-1) and its ligand (sPD-L1) might be potential biomarkers for evaluating the curative efficacy of chemotherapy and patient prognosis in several cancers but not yet in breast cancer.

Author Correction: Invasion of white matter tracts by glioma stem cells is regulated by a NOTCH1-SOX2 positive-feedback loop.

The original and corrected figures are shown in the accompanying Author Correction.

Invasion of white matter tracts by glioma stem cells is regulated by a NOTCH1-SOX2 positive-feedback loop.

Early invasive growth along specific anatomical structures, especially the white matter tract, is regarded as one of the main causes of poor therapeutic outcome of people with gliomas. We show that some glioma stem cells (GSCs) are preferentially located along white matter tracts, which exhibit a demyelinated phenotype, at the invasive frontier of glioma tissues. These GSCs are CD133Notch1, whereas the nerve fibers express the Notch ligand Jagged1.

Targeting different domains of gap junction protein to control malignant glioma.

A rational treatment strategy for glioma, the most common primary central nervous system tumor, should focus on early invasive growth and resistance to current therapeutics. Connexin 43 (Cx43), a gap junction protein, plays important roles not only in the development of the central nervous system and but also in the progression of glioma. The different structural domains of Cx43, including extracellular loops, transmembrane domains, and an intracellular carboxyl terminal, have distinct functions in the invasion and proliferation of gliomas.