# SENP6, a novel p53 negative regulator, is an important new player in cancer

> **NIH NIH R01** · RBHS -CANCER INSTITUTE OF NEW JERSEY · 2021 · $363,713

## Abstract

Abstract
Tumor suppressor p53 plays a key role in tumor suppression. p53 function is frequently impaired in cancer by
mutation or other mechanisms, such as overexpression of negative regulators for p53, which contributes
greatly to tumorigenesis. Cancer cells often display increased de novo fatty acid (FA) synthesis, which is
critical for continued growth and proliferation of cancer cells. Colorectal cancer (CRC) is the third most
commonly diagnosed cancer and the third leading cancer death in the United States. Further understanding
the molecular mechanisms for colorectal tumorigenesis will provide novel strategies for cancer therapy. To
identify novel genes that are critical for CRC development, we performed a large-scale unbiased in vivo RNA
interference screen, and identified SUMO-Specific Protease SENP6 as a novel gene critical for colorectal
tumorigenesis. Currently, the role and its mechanism of SENP6 in colorectal tumorigenesis are unclear. Our
preliminary studies showed that SENP6 is frequently overexpressed in CRC, and its overexpression is
associated with poor prognosis in CRC. Our preliminary results further strongly suggest that SENP6
overexpression plays a critical role in promoting tumor growth in CRC through inhibition of p53 function and
activation of FA synthesis in CRC cells. Based on our preliminary results, we hypothesize that SENP6 plays
an unidentified and critical role in promoting tumorigenesis in CRC through inhibiting p53 function and
promoting FA synthesis. The goal of this proposed study is to determine the role of SENP6 in colorectal
tumorigenesis and its underlying mechanisms, and furthermore, to test the potential therapeutic intervention
targeting CRC with SENP6 overexpression. We will test our hypothesis by following specific aims. Aim 1. To
determine the role of SENP6 in colorectal tumorigenesis in mouse models. Aim 2. To determine the
mechanisms by which SENP6 promotes colorectal tumorigenesis and the potential application of SENP6 in
CRC therapy. Aim 2 has following 2 sub-aims. 2A) To test the hypothesis that SENP6 downregulates p53 to
promote colorectal tumorigenesis. 2B) To determine the role and mechanism of SENP6 in FA synthesis in
CRC and its contribution to colorectal tumorigenesis. We will further test whether pharmacological reactivation
of p53 and inhibition of FA synthesis is a potential therapeutic strategy for CRC with SENP6 overexpression.
It is our expectation that this proposed study will reveal the critical role and mechanism of SENP6 in colorectal
tumorigenesis, and the results from this study will have the potential to lead to the development of novel
targets and strategies for CRC therapy.

## Key facts

- **NIH application ID:** 10197830
- **Project number:** 5R01CA214746-04
- **Recipient organization:** RBHS -CANCER INSTITUTE OF NEW JERSEY
- **Principal Investigator:** Zhaohui Feng
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $363,713
- **Award type:** 5
- **Project period:** 2018-07-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10197830

## Citation

> US National Institutes of Health, RePORTER application 10197830, SENP6, a novel p53 negative regulator, is an important new player in cancer (5R01CA214746-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10197830. Licensed CC0.

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