# Basal Cell Polarity Proteins in Normal Tissue Homeostasis and Cancer

> **NIH NIH R01** · FRED HUTCHINSON CANCER RESEARCH CENTER · 2020 · $402,600

## Abstract

Normal tissue homeostasis is maintained by adult stem and progenitor cells that use cell intrinsic
mechanisms and information from their microenvironment to execute a very complex specialized type
of mitosis known as asymmetric cell division. Two resulting from this division daughter cells acquire
different cell fates. While one cell continues proliferation, another daughter cell withdraws from the stem
cell niche, remodels its intercellular interactions and starts a program which ultimately leads to the cell
cycle withdrawal and differentiation. This process ensures that only the necessary number of cells is
produced at any given time and the cell death and depletion in each tissue is balanced by the birth of
new cells. Defective asymmetric cell division can result in the failure of normal tissue homeostasis and
birth of cancer stem cells, which cannot produce daughters that can properly withdraw from the cell
cycle and differentiate. While asymmetric cell division plays a pivotal role in tissue homeostasis, little
is known about its mechanisms in mammalian organisms. Studies in model organisms revealed critical
role of intercellular interactions and apical-basal cell polarity in regulation of asymmetric cell division.
In Drosophila, basal cell polarity gene lethal giant larvae (lgl) was identified as an important regulator
of asymmetric cell division, and mutations in lgl result in overproduction of dividing stem cells and
development of cancer. Mammalian genomes contain two lgl orthologs Llgl1 and Llgl2. While previous
studies of LLGL1 and LLGL2 in cancer cell lines indicated their potential role as tumor suppressors,
genetic analysis of these genes in mice was complicated by the genetic redundancy and lethality of Llgl
mutants. We have now generated conditional, tissue specific Llgl1/2 double knockout mice. Our
preliminary experiments revealed tumor-suppressive function of Llgl1/2 in skin squamous cell
carcinoma. In this grant, we propose to use our mutant animals, primary cell cultures and in utero
lentiviral transduction of skin epidermis to reveal the role and molecular mechanisms of Llgl gene family
in stem and progenitor cells during normal tissue homeostasis and cancer. These studies will help to
understand the mechanisms of mammalian stem and progenitor cells self-renewal and differentiation
and the role of these mechanisms in cancer.

## Key facts

- **NIH application ID:** 9948601
- **Project number:** 5R01CA234050-02
- **Recipient organization:** FRED HUTCHINSON CANCER RESEARCH CENTER
- **Principal Investigator:** VALERI VASIOUKHIN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $402,600
- **Award type:** 5
- **Project period:** 2019-06-07 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9948601

## Citation

> US National Institutes of Health, RePORTER application 9948601, Basal Cell Polarity Proteins in Normal Tissue Homeostasis and Cancer (5R01CA234050-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9948601. Licensed CC0.

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