# Maintenance of Chromosome Stability by the Hippo Tumor Suppressor Pathway

> **NIH NIH R01** · BOSTON UNIVERSITY MEDICAL CAMPUS · 2020 · $330,000

## Abstract

Chromosome instability (CIN), broadly defined as the persistent acquisition of both numerical and structural
chromosome aberrations, is a hallmark of solid tumors that is known to facilitate tumor initiation, progression, and
relapse. Consequently, CIN confers poor clinical prognosis. The development of CIN is a multistep process: cells
must not only acquire the genetic and/or cell biological defects that induce abnormal chromosome segregation,
but they must also overcome the stresses imposed by aneuploidy that act to restrain subsequent proliferation.
Over the past decade, significant efforts have focused on identifying the underlying mechanisms that produce
chromosome missegregation in cancer cells. However, there remains a paucity of data describing the
mechanisms that respond to abnormalities in chromosome number and limit proliferation. Consequently, how
cells adapt to overcome these growth barriers in order to become CIN remains a key unresolved question in
cancer cell biology. We recently discovered that the Hippo tumor suppressor pathway is activated following
cytokinesis failure and that this limits the proliferation of the resulting tetraploid cells. In addition, our
preliminary data suggest that inactivation of Hippo signaling is sufficient to promote CIN in non-transformed
cells. Together, these findings suggest that the Hippo pathway may have a broadly relevant role in restraining
the growth of cells harboring numerical chromosome abnormalities. The goal of this proposal is to elucidate the
mechanistic role of the Hippo pathway in both sensing and responding to abnormal cell division and
aneuploidy. The aims are: 1) To mechanistically define the role of the Hippo pathway in maintaining chromosome
stability; 2) To determine the role of Hippo signaling in setting the mitotic clock; and 3) To identify cancer-relevant
genetic regulators of Hippo pathway signaling.

## Key facts

- **NIH application ID:** 9968412
- **Project number:** 5R01GM117150-05
- **Recipient organization:** BOSTON UNIVERSITY MEDICAL CAMPUS
- **Principal Investigator:** NEIL J. GANEM
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $330,000
- **Award type:** 5
- **Project period:** 2016-09-23 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9968412

## Citation

> US National Institutes of Health, RePORTER application 9968412, Maintenance of Chromosome Stability by the Hippo Tumor Suppressor Pathway (5R01GM117150-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9968412. Licensed CC0.

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