CRLF1 bridges AKT and mTORC2 through SIN1 to inhibit pyroptosis and enhance chemo-resistance in ovarian cancer.

Ovarian cancer, the second most leading cause of gynecologic cancer mortality worldwide, is challenged by chemotherapy resistance, presenting a significant hurdle. Pyroptosis, an inflammation-linked programmed cell death mediated by gasdermins, has been shown to impact chemoresistance when dysregulated. However, the mechanisms connecting pyroptosis to chemotherapy resistance in ovarian cancer are unclear.

Reuterin promotes pyroptosis in hepatocellular cancer cells through mtDNA-mediated STING activation and caspase 8 expression.

Hepatocellular carcinoma (HCC) is the most common form of liver cancer with poor prognosis. The available drugs for advanced HCC are limited and substantial therapeutic advances including new drugs and new combination therapies are still in urgent need. In this study, we found that the major metabolite of Lactobacillus reuteri (L.

rRNA-Derived Small RNA rsRNA-28S Regulates the Chemoresistance of Prostate Cancer Cells by Targeting PTGIS.

Background: rRNA-derived small RNAs (rsRNAs) represent a novel class of small non-coding RNAs (sncRNAs), produced by the specific cleavage of rRNAs; however, their roles in tumor development are unclear. In the present study, we explored the effect of a kind of rsRNA-28S, which originates from 28S rRNA, on the chemoresistance of prostate cancer cells and the mechanisms underlying its effect.

Methods: Quantitative reverse transcription PCR (RT-PCR) was performed to quantify rsRNA-28S levels in serum samples taken from prostate cancer patients.

Ciclopirox Olamine Induces Proliferation Inhibition and Protective Autophagy in Hepatocellular Carcinoma.

Hepatocellular carcinoma is one of the most common fatal malignancies worldwide. Thus far, the hepatocellular carcinoma prognosis has been bleak due to deficiencies in the identification and diagnosis of early hepatocellular carcinoma. Ciclopirox olamine (CPX) is a synthetic antifungal agent and has been considered as an anti-cancer candidate drug recently, though the detailed mechanisms related to its anti-cancer effect in hepatocellular carcinoma have not yet been revealed.

Transfer RNA-derived small RNAs (tsRNAs): Versatile regulators in cancer.

tRNA-derived small RNAs (tsRNAs) represent a novel class of regulatory small non-coding RNAs (sncRNAs), produced by the specific cleavage of transfer RNAs (tRNAs). In recent years, pilot studies one after the other have uncovered the critical roles of tsRNAs in various fundamental biological processes as well as in the development of human diseases including cancer. Based on the newly updated hallmarks of cancer, we provide a comprehensive review regarding the dysregulation, functional implications and complicated molecular mechanisms of tsRNAs in cancer.

ROS generation attenuates the anti-cancer effect of CPX on cervical cancer cells by inducing autophagy and inhibiting glycophagy.

Cervical cancer is one of the most common gynecological malignancies with poor prognosis due to constant chemoresistance and repeated relapse. Ciclopirox olamine (CPX), a synthetic antifungal agent, has recently been identified to be a promising anti-cancer candidate. However, the detailed mechanisms related to its anti-cancer effects remain unclear and need to be further elucidated.

The ROCK-ezrin signaling pathway mediates LPS-induced cytokine production in pulmonary alveolar epithelial cells.

Background: Ezrin/radixin/moesin (ERM) proteins are members of the protein 4.1 superfamily and function as linkers that connect the actin cytoskeleton to the plasma membrane of cells. ERM also play critical role in the Lipopolysaccharide (LPS)-induced inflammatory response.

PRR11 induces filopodia formation and promotes cell motility via recruiting ARP2/3 complex in non-small cell lung cancer cells.

Filopodia, a finger-like structure and actin-rich plasma-membrane protrusion at the leading edge of the cell, has important roles in cell motility. However, the mechanisms of filopodia generation are not well-understood via the actin-related protein 2/3 (ARP2/3) complex in Non-Small Cell Lung Cancer (NSCLC) cells. We previously have demonstrated that PRR11 associates with the ARP2/3 complex to regulate cytoskeleton-nucleoskeleton assembly and chromatin remodeling.

The expression of kappa-opioid receptor promotes the migration of breast cancer cells in vitro.

Background: Opioid receptors are implicated in cell proliferation and cancer migration. However, the effects and underlying mechanisms of opioid receptor κ (OPRK1) in breast cancer remain unknown.

Methods: Small interfering RNA (siRNAs) was used to knockdown the expression of OPRK1.

B-Myb accelerates colorectal cancer progression through reciprocal feed-forward transactivation of E2F2.

B-Myb is an important transcription factor that plays a critical role in gene expression regulation and tumorigenesis. However, its functional implication in colorectal cancer remains elusive. In this study, we found that B-Myb was significantly upregulated at both mRNA and protein levels in colorectal cancer samples compared to non-tumor counterparts.

DJ-1 promotes epithelial-to-mesenchymal transition via enhancing FGF9 expression in colorectal cancer.

Tumor metastasis is the main contributor to high recurrence and mortality in colorectal cancer (CRC). In a previous study, we found that DJ-1 plays an important role in CRC metastasis, and is the main target in Ciclopirox olamine (CPX)-treated CRC. However, the mechanism underlying DJ-1-induced CRC metastasis remains elusive.

Proline-rich 11 (PRR11) drives F-actin assembly by recruiting the actin-related protein 2/3 complex in human non-small cell lung carcinoma.

The actin cytoskeleton is extremely dynamic and supports diverse cellular functions in many physiological and pathological processes, including tumorigenesis. However, the mechanisms that regulate the actin-related protein 2/3 (ARP2/3) complex and thereby promote actin polymerization and organization in cancer cells are not well-understood. We previously implicated the proline-rich 11 (PRR11) protein in lung cancer development.

Identification and characterization of the promoter of cancer-related gene LOXL2.

Lysyl oxidase like 2, LOXL2, as a member of the lysyl oxidase (LOX) family, has been shown to function similarly to LOX in the extracellular matrix (ECM) by promoting crosslinking of collagen and elastin. LOXL2 is also engaged to transcription regulation, cell signaling transduction and cell adhesion regulation. It has been reported that LOXL2 is highly expressed in several types of tumors and promotes cell proliferation and migration in various cancer cells.

CPX Targeting DJ-1 Triggers ROS-induced Cell Death and Protective Autophagy in Colorectal Cancer.

Colorectal cancer (CRC) is one of the most common cancers worldwide. Ciclopirox olamine (CPX) has recently been identified to be a promising anticancer candidate; however, novel activities and detailed mechanisms remain to be uncovered. The cytotoxic potential of CPX towards CRC cells was examined and .

Tubeimoside-I sensitizes colorectal cancer cells to chemotherapy by inducing ROS-mediated impaired autophagolysosomes accumulation.

Background: Tubeimoside-I (TBM), a plant-derived bioactive compound, shows antitumor activity in different tumors and can enhance the efficacy of chemotherapeutic agents. However, the detail mechanism underlying remains to be elucidated.

Methods: The cytotoxic potential of TBM towards CRC cells was examined by CCK8 assay, colony formation, LDH release assay, flow cytometry method and Western blots.

Repurposing Brigatinib for the Treatment of Colorectal Cancer Based on Inhibition of ER-phagy.

: The sustained and severe endoplasmic reticulum (ER) stress in cancer cells may contribute to apoptotic cell death, thus representing a potential target for cancer therapy. Brigatinib is an anaplastic lymphoma kinase (ALK) inhibitor approved for the treatment of ALK-positive non-small-cell lung cancer (NSCLC). However, it remains unclear if brigatinib has alternative model of action to exert antitumor effect in ALK-negative cancers.

MCT1 relieves osimertinib-induced CRC suppression by promoting autophagy through the LKB1/AMPK signaling.

Colorectal cancer (CRC) is one of the most frequently diagnosed cancers worldwide. Development of novel chemotherapeutics is still required to enable successful treatment and improve survival for CRC patients. Here, we found that osimertinib (OSI) exhibits potent anti-CRC effects by inducing apoptosis, independent of its selective inhibitory activity targeting the EGFR T790M mutation.

Regorafenib induces lethal autophagy arrest by stabilizing PSAT1 in glioblastoma.

GBM (glioblastoma multiforme) is the most common and aggressive brain tumor with no curative options available. Therefore, it is imperative to develop novel potent therapeutic drugs for GBM treatment. Here, we show that regorafenib, an oral multi-kinase inhibitor, exhibits superior therapeutic efficacy over temozolomide, the first-line chemotherapeutic agent for GBM treatment both and .

Cell-surface translocation of annexin A2 contributes to bleomycin-induced pulmonary fibrosis by mediating inflammatory response in mice.

Bleomycin, a widely used anti-cancer drug, may give rise to pulmonary fibrosis, a serious side effect which is associated with significant morbidity and mortality. Despite the intensive efforts, the precise pathogenic mechanisms of pulmonary fibrosis still remain to be clarified. Our previous study showed that bleomycin bound directly to annexin A2 (ANXA2, or p36), leading to development of pulmonary fibrosis by impeding transcription factor EB (TFEB)-induced autophagic flux.

Targeting Metabolic-Redox Circuits for Cancer Therapy.

Metabolic alterations and elevated levels of reactive oxygen species (ROS) are two characteristics of cancer. The metabolic patterns of cancer cells are elaborately reprogrammed to fulfill the high biomass demands of rapid propagation. ROS, the byproducts of metabolic processes, are accumulated in cancer cells partially due to metabolic abnormalities or oncogenic mutations.

Redox signaling and unfolded protein response coordinate cell fate decisions under ER stress.

Endoplasmic reticulum (ER) is a dynamic organelle orchestrating the folding and post-translational maturation of almost all membrane proteins and most secreted proteins. These proteins synthesized in the ER, need to form disulfide bridge to acquire specific three-dimensional structures for function. The formation of disulfide bridge is mediated via protein disulfide isomerase (PDI) family and other oxidoreductases, which contribute to reactive oxygen species (ROS) generation and consumption in the ER.

Tubeimoside I induces accumulation of impaired autophagolysosome against cervical cancer cells by both initiating autophagy and inhibiting lysosomal function.

Cervical cancer is one of the most aggressive human cancers with poor prognosis due to constant chemoresistance and repeated relapse. Tubeimoside I (TBM) has been identified as a potent antitumor agent that inhibits cancer cell proliferation by triggering apoptosis and inducing cell cycle arrest. Nevertheless, the detailed mechanism remains unclear and needs to be further elucidated, especially in cervical cancer.

Ketoconazole exacerbates mitophagy to induce apoptosis by downregulating cyclooxygenase-2 in hepatocellular carcinoma.

Background & Aims: Hepatocellular carcinoma (HCC) is a common cancer worldwide and remains a major clinical challenge. Ketoconazole, a traditional antifungal agent, has attracted considerable attention as a therapeutic option for cancer treatment. However, its mechanism of action is still not clearly defined.