Targeting RBM39 suppresses tumor growth and sensitizes osteosarcoma cells to cisplatin.

Osteosarcoma is one of the most common malignant primary bone tumors and lacks effective therapeutic targets. Recent studies have reported that RNA binding proteins (RBPs) could serve as promising therapeutic targets for cancers, as their critical roles in transcriptional regulation and RNA splicing. Nevertheless, the potential of pharmacologically inhibiting RBPs as a therapeutic strategy for patients with osteosarcoma remains unclear.

The KLF16/MYC feedback loop is a therapeutic target in bladder cancer.

Background: Bladder cancer (BLCA) is a common malignancy characterized by dysregulated transcription and a lack of effective therapeutic targets. In this study, we aimed to identify and evaluate novel targets with clinical potential essential for tumor growth in BLCA.

Methods: CRISPR-Cas9 screening was used to identify transcription factors essential for bladder cancer cell viability.

Targeting the KAT8/YEATS4 Axis Represses Tumor Growth and Increases Cisplatin Sensitivity in Bladder Cancer.

Bladder cancer (BC) is one of the most common tumors characterized by a high rate of relapse and a lack of targeted therapy. Here, YEATS domain-containing protein 4 (YEATS4) is an essential gene for BC cell viability using CRISPR-Cas9 library screening is reported, and that HUWE1 is an E3 ligase responsible for YEATS4 ubiquitination and proteasomal degradation by the Protein Stability Regulators Screening Assay. KAT8-mediated acetylation of YEATS4 impaired its interaction with HUWE1 and consequently prevented its ubiquitination and degradation.

Augmenting L3MBTL2-induced condensates suppresses tumor growth in osteosarcoma.

Osteosarcoma is a highly aggressive cancer and lacks effective therapeutic targets. We found that L3MBTL2 acts as a tumor suppressor by transcriptionally repressing in osteosarcoma. L3MBTL2 recruits the components of Polycomb repressive complex 1.

Targeting the Lysosomal Degradation of Rab22a-NeoF1 Fusion Protein for Osteosarcoma Lung Metastasis.

Rab22a-NeoF fusion protein has recently been reported as a promising target for osteosarcoma lung metastasis. However, how this fusion protein is regulated in cells remains unknown. Here, using multiple screenings, it is reported that Rab22a-NeoF1 fusion protein is degraded by an E3 ligase STUB1 via the autophagy receptor NDP52-mediated lysosome pathway, which is facilitated by PINK1 kinase.

Rab22a-NeoF1 fusion protein promotes osteosarcoma lung metastasis through its secretion into exosomes.

It remains unknown for decades how some of the therapeutic fusion proteins positive in a small percentage of cancer cells account for patient outcome. Here, we report that osteosarcoma Rab22a-NeoF1 fusion protein, together with its binding partner PYK2, is sorted into exosomes by HSP90 via its KFERQ-like motif (RVLFLN). The exosomal Rab22a-NeoF1 fusion protein facilitates the pulmonary pre-metastatic niche formation by recruiting bone marrow-derived macrophages.

Author Correction: Chromosomal translocation-derived aberrant Rab22a drives metastasis of osteosarcoma.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Chromosomal translocation-derived aberrant Rab22a drives metastasis of osteosarcoma.

Osteosarcoma is a type of aggressive malignant bone tumour that frequently metastasizes to lungs, resulting in poor prognosis. However, the molecular mechanisms of lung metastasis of osteosarcoma remain poorly understood. Here we identify exon-intron fusion genes in osteosarcoma cell lines and tissues.

YTHDF2 suppresses cell proliferation and growth via destabilizing the EGFR mRNA in hepatocellular carcinoma.

N-methyladenosin (mA) is one of the most pervasive modification of mRNA in eukaryotes and the mA methyltransferases and demethylases play critical roles in many types of cancer. However the role of mA-binding proteins in cancer remains elusive. Here we report that the down-regulation of YTHDF2 was specifically induced by hypoxia in hepatocellular carcinoma (HCC) cells, and that overexpression of YTHDF2 suppressed cell proliferation, tumor growth and activation of MEK and ERK in HCC cells.

Glipizide suppresses prostate cancer progression in the TRAMP model by inhibiting angiogenesis.

Drug repurposing of non-cancer drugs represents an attractive approach to develop new cancer therapy. Using the TRAMP transgenic mouse model, glipizide, a widely used drug for type 2 diabetes mellitus, has been identified to suppress prostate cancer (PC) growth and metastasis. Angiogenesis is intimately associated with various human cancer developments.

SAP deficiency mitigated atherosclerotic lesions in ApoE(-/-) mice.

Objective: Serum amyloid P conpoent (SAP), a member of the pentraxin family, interact with pathogens and cell debris to promote their removal by macrophages and neutrophils and is co-localized with atherosclerotic plaques in patients. However, the exact mechanism of SAP in atherogenesis is still unclear. We investigated whether SAP influence macrophage recruitment and foam cell formation and ultimately affect atherosclerotic progression.

Inactivation of PI3Kδ induces vascular injury and promotes aneurysm development by upregulating the AP-1/MMP-12 pathway in macrophages.

Objective: An aneurysm is an inflammatory vascular condition. Phosphatidylinositol 3-kinases δ is highly expressed in leukocytes, and play a key role in innate immunity. However, the link between phosphatidylinositol 3-kinases δ and aneurysm development has not yet been elucidated.