# Regulation of Human Tumorigensis by Cancer Specific NXF1 Adaptor Proteins

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2023 · $354,197

## Abstract

Project Summary/Abstract
Background: Cancer originates from genetic alterations that lead to changes in gene
expression programs that promote tumor survival, growth, motility and inhibits
differentiation and apoptosis. The mRNAs from this oncogenic gene expression program
must be exported to the cytoplasm to be translated into protein in order to promote
tumorigenesis. Whether there is regulation of export of tumor specific mRNAs and the
potential proteins involved in this process is unknown. We have shown that tumor
specific NXF1 adaptor proteins regulate export of oncogenic mRNAs. The adaptor
proteins are also highly upregulated during tumor initiation and knockdown of specific
adaptors inhibit tumorigenesis.
Objective/hypothesis: This proposal seeks to understand the molecular mechanisms
driving the progression from normal to neoplastic skin using a RAS driven human
epidermal tumor model. Our preliminary data suggests that 4 adaptor proteins are highly
upregulated during tumor initiation that associates with NXF1 to mediate the export of
the oncogenic gene expression program. Our objective is to characterize the role of
each tumor induced NXF1 adaptor protein in the progression of normal to neoplastic
skin. Furthermore we seek to determine the specific transcripts that each adaptor protein
binds during tumor initiation to promote tumorigenesis.
Specific Aims: (1) To determine the role of NXF1 adaptor proteins in the progression
from normal to neoplastic skin and (2) to identify the transcripts associated with NXF1
adaptor proteins and determine which bound transcripts are exported.
Study Design: To study epidermal tumorigenesis in a more clinically relevant setting,
we generate 3-dimensionally intact human skin, containing human epidermal cells (that
have been permanently knocked down for adaptor proteins) in the context of human
dermal stroma and basement membrane, regenerated on immune compromised mice.
By using this model, we can perform loss of function experiments on NXF1 adaptor
proteins in regenerated human skin to characterize their role in epidermal growth,
differentiation, and progression to neoplasia. We will use CLIP-Seq to determine the
RNAs associated with each adaptor protein during the progression from normal to
neoplastic epidermis.

## Key facts

- **NIH application ID:** 10596156
- **Project number:** 5R01CA269303-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** GEORGE L SEN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $354,197
- **Award type:** 5
- **Project period:** 2022-04-01 → 2027-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10596156

## Citation

> US National Institutes of Health, RePORTER application 10596156, Regulation of Human Tumorigensis by Cancer Specific NXF1 Adaptor Proteins (5R01CA269303-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10596156. Licensed CC0.

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