# The non-canonical Collagen I-DDR1 signaling regulating protein synthesis during metastasis

> **NIH NIH F31** · CEDARS-SINAI MEDICAL CENTER · 2023 · $41,294

## Abstract

PROJECT SUMMARY
The activation of signaling tumor cells via the tumor micrenvironment (TME) to undergo metastasis in bladder
cancer is understudied. Clinically, increased Col I deposition correlates with bladder cancer progression (i.e.
increasing tumor stage). Our published study demonstrated that Col I induces bladder tumor cells to invade and
colonize the lung through Discoidin Domain Receptor 1 (DDR1) pathway. Yet, increase Col deposition is known
to cause nutrient deprivation which is unsustainable for tumor growth. Tumors can adapt to these increasingly
harsh environment by downregulating protein synthesis – a metabolically expensive homeostatic process.
Interestingly, this downregulation of protein synthesis has also been shown to promote resistance to anoikis, cell
death resulting from extracellular matrix detachment, which cancer cells must overcome when they undergo
metastasis. To our knowledge, whether collagen outside-in signaling senses nutrient deprivation and thereafter
reduces energy expenditure by attentuating protein synthesis has yet to be investigated. Interestingly, my pilot
studies show two independent, yet complementary non-canonical mechanisms of downregulating protein
synthesis, which involves Col I-DDR1 interaction. I now propose to 1) interrogate these two mechanisms that
downregulate protein synthesis and 2) how this Col I-DDR1 mediated downregulation of protein synthesis affects
the efficiency of cancer metastasis. Knowledge gained from the success of this proposal will yield newer insights
on Col I-DDR1 interaction in promoting cancer cell survival and metastasis in bladder cancer.

## Key facts

- **NIH application ID:** 10607947
- **Project number:** 1F31CA278582-01
- **Recipient organization:** CEDARS-SINAI MEDICAL CENTER
- **Principal Investigator:** Mark E. Alonzo
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $41,294
- **Award type:** 1
- **Project period:** 2023-12-22 → 2026-12-21

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10607947

## Citation

> US National Institutes of Health, RePORTER application 10607947, The non-canonical Collagen I-DDR1 signaling regulating protein synthesis during metastasis (1F31CA278582-01). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10607947. Licensed CC0.

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