# Circadian Clock Disruption and Colorectal Cancer

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA-IRVINE · 2020 · $358,375

## Abstract

PROJECT SUMMARY/ABSTRACT
 Colorectal cancer (CRC) is the third leading cause of cancer-related deaths and
the third most commonly diagnosed cancer in the United States. Despite the advantages
of polyp screening for early detection, treatment options for advanced CRC rely on
aggressive chemotherapy. Therefore, targeted therapy for the treatment of CRC is
critically needed. Strikingly, clinical evidence has shown that compared to normal
intestinal tissue, human colorectal tumors exhibit a down-regulation of gene expression
of all components of the circadian clock molecular machinery. The circadian clock is the
endogenous biological pacemaker which controls several physiological, endocrine and
metabolic processes that operate to maintain organismal homeostasis within a strict 24-
hour period. Several lines of evidence suggest that disruption of circadian rhythms
results in cancer, yet the precise molecular mechanisms and detailed signaling
pathways have yet to be elucidated. Moreover, the crosstalk between the circadian clock
and proliferative pathways in the intestine is not fully elucidated, and more specifically,
how this crosstalk is involved in CRC initiation and progression in vivo remains
unresolved. To address this knowledge gap, we have generated a novel genetically
engineered mouse model (GEMM) to elucidate the effects of circadian clock disruption
on intestinal cell proliferation and CRC. We propose that genetic disruption of the
molecular clock machinery aberrantly drives Wnt/b-Catenin signaling in the intestine.
One goal of this proposal is to delineate the role of the circadian clock on Wnt-
dependent proliferation pathways in the intestine, including pathways that govern
cancer-initiating cell populations. A second goal of this proposal is to define the
molecular mechanism of how the circadian clock impinges on Wnt/b-Catenin dependent
transcriptional and epigenetic pathways. Our studies have important clinical implications
in understanding how disruption of the biological pacemaker, on the molecular level,
alters tumor initiation and disease progression to CRC. These findings provide novel
insight into the potential for therapeutic targeting of the circadian clock for treatment of
CRC, in addition to other tumors types dependent on activated Wnt signaling.

## Key facts

- **NIH application ID:** 9864950
- **Project number:** 1R01CA244519-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA-IRVINE
- **Principal Investigator:** Selma Masri
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $358,375
- **Award type:** 1
- **Project period:** 2020-03-01 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9864950

## Citation

> US National Institutes of Health, RePORTER application 9864950, Circadian Clock Disruption and Colorectal Cancer (1R01CA244519-01). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9864950. Licensed CC0.

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