# The mechanism of SOX2 in the development of neuroendocrine lineages and its regulation of cell pliancy

> **NIH NIH P20** · SANFORD RESEARCH/USD · 2020 · $306,203

## Abstract

PROJECT SUMMARY 
 Cancer, especially pediatric cancer, is a devastating diseases effecting a broad swath of humanity and 
consequently we must be able to understand the development of cancer in a holistic manner to develop the next 
generation of therapies. While there has been significant progress in elucidating genetic mutations which drive 
cancer initiation, many genetically engineered mouse models of cancer have indicated that necessary genetic 
mutations are oftentimes insufficient for tumor formation, i.e. not all cells harboring the necessary mutations form 
a tumor. Therefore, there must be other factors which license a cell with the capacity to form a tumor when the 
necessary mutations are present. We hypothesize that these cells are licensed as a consequence of the prior 
development of the cell. A cell's development is guided in large part by master regulators which are the key 
genes to define cell identity. As master regulators can induce cells to switch identity, a process known as 
reprogramming and which shares many characteristics to tumor initiation, we expect that misregulation of master 
regulators throughout development may be involved in the licensing of cells for cancer formation. We have shown 
that the master regulator, Sox2, is required for the formation of tumors that are initiated by the loss of the 
retinoblastoma tumor suppressor (Rb). Notably Sox2 is the master regulator to define the few cell types which 
form tumors when Rb is lost, most commonly neuroendocrine cells. We will therefore investigate the regulation 
of Sox2 during development in these neuroendocrine lineages and determine if misregulation of Sox2 is 
responsible for cancer licensing. We will pursue this investigation by pursuing the following aims: 1) To 
understand the mechanism of Sox2 regulation during development and how this goes awry in tumor formation, 
and 2) To determine if Sox2 derepressed cells are tumor initiating upon Rb-loss. We anticipate that the 
successful completion of these aims will lead to a greater understanding of how development might induce 
cancer later in life, and provide new avenues for cancer therapies and preventation.

## Key facts

- **NIH application ID:** 10004075
- **Project number:** 5P20GM103620-08
- **Recipient organization:** SANFORD RESEARCH/USD
- **Principal Investigator:** Michael S. Kareta
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $306,203
- **Award type:** 5
- **Project period:** — → —

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10004075

## Citation

> US National Institutes of Health, RePORTER application 10004075, The mechanism of SOX2 in the development of neuroendocrine lineages and its regulation of cell pliancy (5P20GM103620-08). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10004075. Licensed CC0.

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