Abstract. Aging is a critical yet understudied determinant in pancreatic ductal adenocarcinoma (PDAC) risk and outcomes. Despite a strong epidemiological association with age, conventional PDAC precli...

Chen et al. identify two distinct antigen-presenting cancer-associated fibroblast (apCAF) populations across multiple cancer types. Mesothelial-related apCAFs locate near cancer cells while fibrocyte-...

The Gerstner Sloan Kettering Graduate School of Biomedical Sciences offers the next generation of basic scientists a program to study the biological sciences through the lens of cancer

PI5P4Kα is a critical metabolic gatekeeper in PDAC, promoting glucose and iron acquisition to support tumor survival. Arora et al. demonstrate that PI5P4Kα suppression disrupts the metabolic flexibili...

Mechanical confinement of cancer cells at the tumour–microenvironment interface induces phenotype switching through chromatin remodelling by HMGB2, leading to a more invasive and drug-resistant state ...

Mechanical confinement of cancer cells at the tumour–microenvironment interface induces phenotype switching through chromatin remodelling by HMGB2, leading to a more invasive and drug-resistant state ...

An NNMT inhibitor reduces tumour burden and metastasis in multiple mouse cancer models and restores immune checkpoint blockade efficacy by decreasing cancer-associated-fibroblast-mediated recruitment ...

More than 2,700 human mRNA 3′UTRs have hundreds of highly conserved (HC) nucleotides, but their biological roles are unclear. Here, we show that mRNAs with HC 3′UTRs mostly encode proteins with long intrinsically disordered regions (IDRs), including MYC, UTX, and JMJD3. These proteins are only fully active when translated from mRNA templates that include their 3′UTRs, raising the possibility of functional interactions between 3′UTRs and IDRs. Rather than affecting protein abundance or localization, we find that HC 3′UTRs control transcriptional or histone demethylase activity through co-translationally determined protein oligomerization states that are kinetically stable. 3′UTR-dependent changes in protein folding require mRNA-IDR interactions, suggesting that mRNAs act as IDR chaperones. These mRNAs are multivalent, a biophysical RNA feature that enables their translation in network-like condensates, which provide favorable folding environments for proteins with long IDRs. These data indicate that the coding sequence is insufficient for the biogenesis of biologically active conformations of IDR-containing proteins and that RNA can catalyze protein folding. ### Competing Interest Statement The authors have declared no competing interest. Pershing Square Foundation, https://ror.org/04tce9s05 G. Harold & Leila Y. Mathers Foundation National Institutes of Health, DP1GM123454, R35GM144046 Memorial Sloan Kettering Cancer Center, https://ror.org/02yrq0923, P30 CA008748

The U.S. government has sought to restrict immigration under the “America First” doctrine. These policies severely harm American science by stripping it of talent and eliminating a major driver of its...

Secretion of ligands of the human epidermal growth factor (EGFR) family of receptors or erythroblastic leukemia viral oncogene family (ERBB1-4) is a feature common to many cancer cells. However, our u...

Normal pancreatic mesenchyme expresses stem cell factor (KITL), which is lost in the cancer-associated fibroblast state during tumorigenesis and restrains pancreatic inflammation, epithelial identity,...

Metastasis is the leading cause of cancer deaths; nonetheless, how tumor cells adapt to vastly different organ contexts is largely unknown. To investigate this question, we generated a transcriptomic ...

By blocking announcements in the Federal Register, the administration is keeping experts from meeting to evaluate funding proposals.

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