# Amyloid-bodies and the Evolution of Malignancies

> **NIH NIH R01** · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · 2024 · $76,750

## Abstract

Diversity Supplement Project Summary
The ability of cancer cells to adapt to a wide variety of stress conditions plays a critical role in various
physiological facets of tumorigenesis. We recently reported the discovery of stress-induced noncoding RNA
derived from stimuli-specific loci of the ribosomal intergenic spacer (rIGSRNA); an enigmatic region of the human
genome historically dismissed as “junk” DNA. We showed that rIGSRNA activate a physiological amyloidogenic
program that converts nucleoli into Amyloid-bodies: reversible nuclear membrane-less compartments composed
of immobilized proteins in an amyloid-like state. While many cellular bodies have been described as liquid-like
(e.g., stress granules, P-bodies, germ cell granules), the discovery of Amyloid-bodies provided evidence of an
amyloidogenic program that can physiologically transition biological matter to a solid state. Amyloid-bodies are
found in sub-populations of cells in normal tissues, the core of low-grade human tumors and cells responding to
various stimuli highlighting their ubiquitous nature. Proteomic analysis revealed that Amyloid-bodies immobilize
participants of the DNA synthesis machinery and cell cycle control, amongst many other metabolic regulators.
Intriguingly, Amyloid-bodies share many biophysical properties with the amyloidogenic, solid-like Balbiani-bodies
involved in metabolic suppression in Xenopus. Likewise, yeast solidify elements of their proteome to sporulate
and arrest growth in non-permissive conditions. This raises the fascinating possibility that stressed cancer cells
assemble Amyloid-bodies to enter a spore-like state of extreme metabolic depression.
We recently showed that rIGSRNA coordinate a RNA tailing program mediated by their interactions to Terminal
NucleotidylTransferases 4b (TENT4b) to drive Amyloid-bodies biogenesis. This post-translational pathway
enables cancer cells to immobilize elements of the DNA synthesis machinery and halt oncogenic signaling in an
adaptive response to severe environmental insults In this Diversity Supplement Proposal, Ms. Rios will focus her
efforts on three goals that a included in Specific Aim #2 and #3 of the Parental NCI R01. Based on these
preliminary and published results, we hypothesize that “RNA tailing program drives amyloidogenic phase
transition to induce metabolic suppression of cancer cells”. We plan to test this hypothesis by: 1- Test the
role of rIGSRNA/TENT4b interactions in phase transition and 2- Examine the role of phase transition in clinical
samples and orthotopic tumor models. The discovery of dedicated enzymatic programs that drive physiological
amyloidogenesis provides a unique opportunity to study the role of liquid-to-solid phase transition in human
clinical samples and in vivo tumor assays. By studying clinical samples, in culture and orthotopic animal models,
we will test if phase transition induces a unique and yet uncharacterized cancer cell state of extreme metabolic
depression, while...

## Key facts

- **NIH application ID:** 11063373
- **Project number:** 3R01CA275828-02S1
- **Recipient organization:** UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
- **Principal Investigator:** Stephen Lee
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $76,750
- **Award type:** 3
- **Project period:** 2023-08-07 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11063373

## Citation

> US National Institutes of Health, RePORTER application 11063373, Amyloid-bodies and the Evolution of Malignancies (3R01CA275828-02S1). Retrieved via AI Analytics 2026-06-16 from https://api.ai-analytics.org/grant/nih/11063373. Licensed CC0.

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