USP33 is an integrin α6 deubiquitinase and promotes esophageal squamous cell carcinoma cell migration and metastasis.

Purpose: The deubiquitinating enzymes (DUBs) have been linked to cancer initiation and progression. Although ubiquitin-specific protease 33 (USP33) represents a significant factor in regulating various tumor cell behaviors, its specific biological functions and precise mechanisms in esophageal squamous cell carcinoma (ESCC) progression remain unclear.

Methods: The expressions of USP33 mRNA in GEO databases, clinical ESCC samples, and USP33 protein were analyzed using bioinformatics, RT-PCR, and immunohistochemistry, respectively.

ROS: A "booster" for chronic inflammation and tumor metastasis.

Reactive oxygen species (ROS) are a group of highly active molecules produced by normal cellular metabolism and play a crucial role in the human body. In recent years, researchers have increasingly discovered that ROS plays a vital role in the progression of chronic inflammation and tumor metastasis. The inflammatory tumor microenvironment established by chronic inflammation can induce ROS production through inflammatory cells.

DePARylation is critical for S phase progression and cell survival.

Poly(ADP-ribose)ylation or PARylation by PAR polymerase 1 (PARP1) and dePARylation by poly(ADP-ribose) glycohydrolase (PARG) are equally important for the dynamic regulation of DNA damage response. PARG, the most active dePARylation enzyme, is recruited to sites of DNA damage via pADPr-dependent and PCNA-dependent mechanisms. Targeting dePARylation is considered an alternative strategy to overcome PARP inhibitor resistance.

Vitamin K: New insights related to senescence and cancer metastasis.

Several clinical trials and experimental studies have recently shown that vitamin K (VK) supplementation benefits the human body. Specifically, VK participates in coagulation and is associated with cellular senescence and cancer. VK has a potential anticancer effect in various cancers, such as pancreatic and prostate cancers.

USP10 promotes migration and cisplatin resistance in esophageal squamous cell carcinoma cells.

Cisplatin-based chemotherapy is the main treatment option for advanced or metastatic esophageal squamous cell carcinoma (ESCC). However, most ESCC patients develop drug resistance within 2 years after receiving cisplatin chemotherapy. Ubiquitin-specific protease 10 (USP10) is abnormally expressed in a variety of cancers, but the mechanistic roles of USP10 in ESCC are still obscure.

DePARylation is critical for S phase progression and cell survival.

Poly(ADP-ribose)ylation or PARylation by PAR polymerase 1 (PARP1) and dePARylation by poly(ADP-ribose) glycohydrolase (PARG) are equally important for the dynamic regulation of DNA damage response. PARG, the most active dePARylation enzyme, is recruited to sites of DNA damage via pADPr-dependent and PCNA-dependent mechanisms. Targeting dePARylation is considered an alternative strategy to overcome PARP inhibitor resistance.

SLC7A11 expression level dictates differential responses to oxidative stress in cancer cells.

The cystine transporter solute carrier family 7 member 11 (SLC7A11; also called xCT) protects cancer cells from oxidative stress and is overexpressed in many cancers. Here we report a surprising finding that, whereas moderate overexpression of SLC7A11 is beneficial for cancer cells treated with HO, a common oxidative stress inducer, its high overexpression dramatically increases HO-induced cell death. Mechanistically, high cystine uptake in cancer cells with high overexpression of SLC7A11 in combination with HO treatment results in toxic buildup of intracellular cystine and other disulfide molecules, NADPH depletion, redox system collapse, and rapid cell death (likely disulfidptosis).

Expression of GnT-III decreases chemoresistance via negatively regulating P-glycoprotein expression: Involvement of the TNFR2-NF-κB signaling pathway.

The phenomenon of multidrug resistance (MDR) is called chemoresistance with respect to the treatment of cancer, and it continues to be a major challenge. The role of N-glycosylation in chemoresistance, however, remains poorly understood. Here, we established a traditional model for adriamycin resistance in K562 cells, which are also known as K562/adriamycin-resistant (ADR) cells.

Prognostic, Diagnostic, and Clinicopathological Significance of Circular RNAs in Pancreatic Cancer: A Systematic Review and Meta-Analysis.

Pancreatic cancer (PC) is a highly aggressive malignant tumor with a high mortality rate. It is urgent to find optimal molecular targets for the early diagnosis and treatment of PC. Here, we aimed to systematically analyze the prognostic, diagnostic, and clinicopathological significance of circular RNAs (circRNAs) in PC.

USP7 substrates identified by proteomics analysis reveal the specificity of USP7.

Deubiquitylating enzymes (DUBs) remove ubiquitin chains from proteins and regulate protein stability and function. USP7 is one of the most extensively studied DUBs, since USP7 has several well-known substrates important for cancer progression, such as MDM2, N-MYC, and PTEN. Thus, USP7 is a promising drug target.

Integrin β1 in Pancreatic Cancer: Expressions, Functions, and Clinical Implications.

Pancreatic cancer (PC) is characterized by rapid progression and a high mortality rate. The current treatment is still based on surgical treatment, supplemented by radiotherapy and chemotherapy, and new methods of combining immune and molecular biological treatments are being explored. Despite this, the survival rate of PC patients is still very disappointing.

TM4SF1 promotes esophageal squamous cell carcinoma metastasis by interacting with integrin α6.

Transmembrane-4 L-six family member-1 (TM4SF1) is a member of the L6 family and functions as a signal transducer to regulate tumor cell behaviors. However, the function and mechanism of TM4SF1 in esophageal squamous cell carcinoma (ESCC) metastasis remains unclear. Here, we find that TM4SF1 expression is increased and positively correlated with clinical TNM stage, N classification, differentiation, tumor size, and poor prognosis in ESCC patients.

Long Non-Coding RNAs in Pancreatic Cancer: Biologic Functions, Mechanisms, and Clinical Significance.

Despite tremendous efforts devoted to research in pancreatic cancer (PC), the mechanism underlying the tumorigenesis and progression of PC is still not completely clear. Additionally, ideal biomarkers and satisfactory therapeutic strategies for clinical application in PC are still lacking. Accumulating evidence suggests that long non-coding RNAs (lncRNAs) might participate in the pathogenesis of diverse cancers, including PC.

A targetable LIFR-NF-κB-LCN2 axis controls liver tumorigenesis and vulnerability to ferroptosis.

The growing knowledge of ferroptosis has suggested the role and therapeutic potential of ferroptosis in cancer, but has not been translated into effective therapy. Liver cancer, primarily hepatocellular carcinoma (HCC), is highly lethal with limited treatment options. LIFR is frequently downregulated in HCC.

Glucocorticoid receptor regulates PD-L1 and MHC-I in pancreatic cancer cells to promote immune evasion and immunotherapy resistance.

Despite unprecedented responses of some cancers to immune checkpoint blockade (ICB) therapies, the application of checkpoint inhibitors in pancreatic cancer has been unsuccessful. Glucocorticoids and glucocorticoid receptor (GR) signaling are long thought to suppress immunity by acting on immune cells. Here we demonstrate a previously undescribed tumor cell-intrinsic role for GR in activating PD-L1 expression and repressing the major histocompatibility complex class I (MHC-I) expression in pancreatic ductal adenocarcinoma (PDAC) cells through transcriptional regulation.

Roles of Integrins in Gastrointestinal Cancer Metastasis.

Integrins are a large family of heterodimeric transmembrane receptors which mediate cell adhesion and transmit signals to the cell interior. The mechanistic roles of integrins have long been an enigma in cancer, given its complexity in regulating different cellular behaviors. Recently, however, increasing research is providing new insights into its function and the underlying mechanisms, which collectively include the influences of altered integrin expression on the aberrant signaling pathways and cancer progression.

Non-canonical function of DGCR8 in DNA double-strand break repair signaling and tumor radioresistance.

In response to DNA double-strand breaks (DSBs), repair proteins are recruited to the damaged sites. Ubiquitin signaling plays a critical role in coordinating protein recruitment during the DNA damage response. Here, we find that the microRNA biogenesis factor DGCR8 promotes tumor resistance to X-ray radiation independently of its Drosha-binding ability.

USP37 is a SNAI1 deubiquitinase.

SNAI1, an epithelial-mesenchymal transition (EMT)-inducing transcription factor, promotes tumor metastasis and resistance to apoptosis and chemotherapy. SNAI1 protein levels are tightly regulated by proteolytic ubiquitination. Here, we identified USP37 as a SNAI1 deubiquitinase that removes the polyubiquitination chain from SNAI1 and prevents its proteasomal degradation.

Identification of the minimal N-glycosylation on integrin α5β1 required for its inhibitory effect on EGFR signaling and cell proliferation.

The N-glycosylation of integrin α5β1 is involved in multiple cell biological functions. Our group previously reported that the N-glycosylation of the Calf-1,2 domain on α5 subunit (S3-5,10-14) was important for its inhibitory effect on EGFR signaling through regulating α5-EGFR complex formation. In this follow-up study, we provide evidence that the N-glycosylation on integrin β1 subunit suppress cell growth by promoting its association with EGFR under fibronectin (FN)-coated conditions.

SKP2- and OTUD1-regulated non-proteolytic ubiquitination of YAP promotes YAP nuclear localization and activity.

Dysregulation of YAP localization and activity is associated with pathological conditions such as cancer. Although activation of the Hippo phosphorylation cascade is known to cause cytoplasmic retention and inactivation of YAP, emerging evidence suggests that YAP can be regulated in a Hippo-independent manner. Here, we report that YAP is subject to non-proteolytic, K63-linked polyubiquitination by the SCF E3 ligase complex (SKP2), which is reversed by the deubiquitinase OTUD1.

ZRANB1 Is an EZH2 Deubiquitinase and a Potential Therapeutic Target in Breast Cancer.

Although EZH2 enzymatic inhibitors have shown antitumor effects in EZH2-mutated lymphoma and ARID1A-mutated ovarian cancer, many cancers do not respond because EZH2 can promote cancer independently of its histone methyltransferase activity. Here we identify ZRANB1 as the EZH2 deubiquitinase. ZRANB1 binds, deubiquitinates, and stabilizes EZH2.

Inhibition of fucosylation by 2-fluorofucose suppresses human liver cancer HepG2 cell proliferation and migration as well as tumor formation.

Core fucosylation is one of the most important glycosylation events in the progression of liver cancer. For this study, we used an easily handled L-fucose analog, 2-fluoro-L-fucose (2FF), which interferes with the normal synthesis of GDP-fucose, and verified its potential roles in regulating core fucosylation and cell behavior in the HepG2 liver cancer cell line. Results obtained from lectin blot and flow cytometry analysis clearly showed that 2FF treatment dramatically inhibited core fucosylation, which was also confirmed via mass spectrometry analysis.