MIIP downregulation drives colorectal cancer progression through inducing peri-cancerous adipose tissue browning.

Background: The enrichment of peri-cancerous adipose tissue is a distinctive feature of colorectal cancer (CRC), accelerating disease progression and worsening prognosis. The communication between tumor cells and adjacent adipocytes plays a crucial role in CRC advancement. However, the precise regulatory mechanisms are largely unknown.

MIIP inhibits clear cell renal cell carcinoma proliferation and angiogenesis negative modulation of the HIF-2α-CYR61 axis.

Objective: In various cancers, migration and invasion inhibitory protein (MIIP) is expressed at low level and is involved in cancer pathogenesis. Herein, we sought to explore the function of MIIP in clear cell renal cell carcinoma (ccRCC).

Methods: CCK-8, colony formation, cell cycle, and endothelial cell tube formation assays were performed to evaluate the roles of MIIP in ccRCC proliferation and angiogenesis.

miR-145-5p Modulates Gefitinib Resistance by Targeting NRAS and MEST in Non-Small Cell Lung Cancer.

Objective: microRNAs may play essential roles in the development and drug resistance of non-small cell lung cancer (NSCLC). However, their functions and mechanisms are not fully understood. Our goal was to define the role of miR-145-5p in the gefitinib resistance of NSCLC.

MIIP inhibits EMT and cell invasion in prostate cancer through miR-181a/b-5p-KLF17 axis.

Growing evidence have shown that the migration and invasion inhibitory protein (MIIP, also known as IIp45) functions as a tumor suppressor and its expression is downregulated in several types of cancer, yet the function of MIIP in prostate cancer (PCa) and the underlying mechanism of action remains largely unknown. Here we demonstrated that MIIP acts as a suppressor of PCa by inhibiting epithelial-mesenchymal transition (EMT) and cell invasion. Overexpressing MIIP repressed cellular invasion of PC3 and DU145 in vitro, accompanied by a decrease of EMT-inducing factors, and an increase of E-cadherin and KLF17.

[RAD51 promotes proliferation and migration of glioblastoma cells and decreases sensitivity of cells to temozolomide].

Objective To investigate the role of RAD51 in cell proliferation, migration and chemosensitivity to temozolomide (TMZ) using U251 glioma cell line, and to clarify the underlying molecular mechanism. Methods TCGA database was utilized to analyze the expression changes of RAD51 in gliomas. RAD51 was over-expressed or knocked down in U251 glioma cells via lentivirus infection, or its activity was inhibited by small molecule inhibitors.

Correction to: MIIP inhibits the growth of prostate cancer via interaction with PP1α and negative modulation of AKT signaling.

Following publication of the original article [1], the authors reported that the given name of Qinhao Wang was incorrectly published as Qinghao Wang. The original article has been corrected.

IDH2 compensates for IDH1 mutation to maintain cell survival under hypoxic conditions in IDH1‑mutant tumor cells.

Mutations of isocitrate dehydrogenase (IDH) 1 and 2 occur in low‑grade gliomas, acute myeloid leukemias and other types of solid cancer. By catalyzing the reversible conversion between isocitrate and α‑ketoglutarate (α‑KG), IDH1 and 2 contribute to the central process of metabolism, including oxidative and reductive metabolism. IDH1 and 2 mutations result in the loss of normal catalytic function and acquire neomorphic activity, facilitating the conversion of α‑KG into an oncometabolite, (R)‑2‑hydroxyglutarate, which can cause epigenetic modifications and tumorigenesis.

MIIP inhibits the growth of prostate cancer via interaction with PP1α and negative modulation of AKT signaling.

Background: Over-activation of phosphatidylinositol 3-kinase (PI3K)-AKT-mammalian target of rapamycin (mTOR) signaling pathway is one of important mechanisms to promote castration resistant prostate cancer, the final stage of prostate cancer (PCa). Dysregulation of PP1-meditaed AKT dephosphorylation might contribute to such an event but is not fully understood. As a newly identified tumor suppressor, MIIP exerts its role in various types of cancer but has not been investigated in PCa.

NDRG2 facilitates colorectal cancer differentiation through the regulation of Skp2-p21/p27 axis.

Poorly differentiated colorectal cancers (CRCs) are more aggressive and lack targeted therapies. We and others previously reported the predominant role of tumor-suppressor NDRG2 in promoting CRC differentiation, but the underlying mechanism is largely unknown. Herein, we demonstrate that NDRG2 induction of CRC cell differentiation is dependent on the repression of E3 ligase Skp2 activity.

GOLM1 promotes prostate cancer progression through activating PI3K-AKT-mTOR signaling.

Background: Prostate cancer (PCa) is the most commonly diagnosed cancer in men. Various molecular mechanisms account for PCa progression and elucidation of these mechanisms is key for selection of optimal therapies and improvement of patient outcome. Golgi membrane protein 1 (GOLM1) has been identified as a novel biomarker for PCa, but its biological functions and molecular mechanisms remain poorly understood.

NDRG2 acts as a PERK co-factor to facilitate PERK branch and ERS-induced cell death.

NDRG2, a newly identified tumor suppressor, is also responsive to various stresses, such as hypoxia and DNA damage. Here, we reported that in human hepatoma SK-Hep-1 and HepG2 cells, NDRG2 mRNA and protein levels were upregulated by different endoplasmic reticulum stress inducers including Tg, Tm, and DTT. Further, using NDRG2-overexpressing hepatoma cell lines and Ndrg2KO mice liver tissues, we found that, among the three branches of unfolded protein response signaling, NDRG2 facilitates protein kinase RNA-like ER kinase (PERK) pathway via interaction with PERK, enhancing its downstream ATF4 and CHOP.

Immunoproapoptotic molecule scFv-Fdt-tBid modified mesenchymal stem cells for prostate cancer dual-targeted therapy.

Highly efficient target therapy is urgently needed for prostate cancer with overexpression of γ-seminoprotein (γ-SM). Recent studies indicated that mesenchymal stem cells (MSCs) are attractive candidate for cell-based, targeted therapy due to their tumor tropism. Here we designed a dual-target therapeutic system in which MSCs were engineered to produce and deliver scFv-Fdt-tBid, a novel γ-SM-targeted immunoproapoptotic molecule.

NDRG2 overexpression suppresses hepatoma cells survival during metabolic stress through disturbing the activation of fatty acid oxidation.

Because of the high nutrient consumption and inadequate vascularization, solid tumor constantly undergoes metabolic stress during tumor development. Oncogenes and tumor suppressor genes participated in cancer cells' metabolic reprogramming. N-Myc downstream regulated gene 2 (NDRG2) is a recently identified tumor suppressor gene, but its function in cancer metabolism, particularly during metabolic stress, remains unclear.

The chimeric ubiquitin ligase SH2-U-box inhibits the growth of imatinib-sensitive and resistant CML by targeting the native and T315I-mutant BCR-ABL.

Chronic myeloid leukemia (CML) is characterized by constitutively active fusion protein tyrosine kinase BCR-ABL. Although the tyrosine kinase inhibitor (TKI) against BCR-ABL, imatinib, is the first-line therapy for CML, acquired resistance almost inevitably emerges. The underlying mechanism are point mutations within the BCR-ABL gene, among which T315I is notorious because it resists to almost all currently available inhibitors.

Functional and clinical evidence that TAZ is a candidate oncogene in hepatocellular carcinoma.

Transcriptional co-activator with PDZ-binding motif (TAZ) has been reported to be associated with carcinogenesis. However, the cellular function of TAZ in human hepatocellular carcinoma (HCC) remains elusive. In this study, an immunohistochemistry analysis revealed that the expression of TAZ in cancer tissue samples from 180 HCC patients was significantly higher than that in adjacent normal tissues.

Chimeric ubiquitin ligases inhibit non-small cell lung cancer via negative modulation of EGFR signaling.

Targeting epidermal growth factor receptor (EGFR) represents a promising therapeutic strategy for non-small cell lung cancers (NSCLC). The ubiquitin-proteasome system (UPS) is a major pathway that mediates protein degradation. To target the degradation of EGFR, we generated two artificial ubiquitin ligases, which are composed of an EGFR-binding domain, i.

Engineered ubiquitin ligase PTB-U-box targets insulin/insulin-like growth factor receptor for degradation and coordinately inhibits cancer malignancy.

The type 1 insulin-like growth factor receptor (IGF-1R) is a promising target for cancer therapy with antibodies and small molecule tyrosine kinase inhibitors (TKIs) which have been actively tested clinically. Evidences have demonstrated that insulin receptor (IR), which is implicated in tumorigenesis, conveys resistance to IGF-1R targeted therapy. This provided the compelling rationale for co-targeting IGF-1R and IR.

Two mature products of MIR-491 coordinate to suppress key cancer hallmarks in glioblastoma.

MIR-491 is commonly co-deleted with its adjacent CDKN2A on chromosome 9p21.3 in glioblastoma multiforme (GBM). However, it is not known whether deletion of MIR-491 is only a passenger event or has an important role.

Up-regulation of pVHL along with down-regulation of HIF-1α by NDRG2 expression attenuates proliferation and invasion in renal cancer cells.

The majority of renal cell carcinomas (RCCs) are characterized by loss of function of the tumor suppressor gene von Hippel Lindau (VHL), which acts as ubiquitin ligase for hypoxia-inducible factor-1α (HIF-1α). In the absence of VHL, HIF-1α protein becomes stabilized and contributes to tumorigenesis. Recent data demonstrate the antitumor efficacy of VHL promoter in RCC cells.