# Role of claudin-1 in Colon Cancer

> **NIH VA I01** · OMAHA VA  MEDICAL CENTER · 2021 · —

## Abstract

The colon cancer (CRC) staging, at the time of disease diagnosis, is critical for patient survival,
which ranges from 90% for patients with localized disease to meagre 13% for the ones with
metastasis. Thus, improved understanding of the molecular regulation of CRC-progression and
metastasis is critical and urgent, to develop novel therapies. In this regard, studies from our,
and other laboratories, have provided strong support for a casual role for upregulated claudin-
1 expression in promoting CRC malignancy, especially metastasis. An upregulated (and
mislocalized) claudin-1 expression in CRC patient samples associated predominantly with CRC
metastasis to liver (58%) and lymph nodes (35%). Moreover, genetic manipulation of claudin-1
expression was sufficient to modulate metastatic ability of CRC cells lines in vitro and in vivo.
Further analysis suggested essential roles of proto-oncogenes Src and EphA2 in claudin-1
mediated CRC progression. The key objectives of this proposal are to determine the roles of Src-
and EphA2-signaling in fostering CRC malignancy under conditions of the dysregulated claudin-
1 expression, and preclinical testing of a novel claudin-1 inhibitor for its therapeutic efficacy in
inhibiting CRC malignancy. To test our hypothesis we propose following studies: Specific Aim-
1. To determine how dysregulated claudin-1 expression promotes dissemination of colon cancer
cell and metastasis; and Specific Aim-2. To test therapeutic efficacy of a novel anti-claudin-1
small molecule inhibitor (I-6) in inhibiting CRC malignancy. The outcome of this study are
expected to have substantial impact on prevention/inhibition of CRC metastasis.

## Key facts

- **NIH application ID:** 10049181
- **Project number:** 5I01BX002086-08
- **Recipient organization:** OMAHA VA  MEDICAL CENTER
- **Principal Investigator:** Punita Dhawan
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2021
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2013-07-01 → 2022-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10049181

## Citation

> US National Institutes of Health, RePORTER application 10049181, Role of claudin-1 in Colon Cancer (5I01BX002086-08). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10049181. Licensed CC0.

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