# Role of Sox2 in Stress Adaptations to Ovarian Cancer Anchorage Independence

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2021 · $370,349

## Abstract

PROJECT SUMMARY
Late stage ovarian cancer is marked by poor patient survival due to metastatic spread in the peritoneal cavity.
Malignant ascites in the peritoneum harbor tumor cells that exhibit adaptability to anchorage independent survival
required for transcoelomic metastasis. Thus, defining key adaptation signals that support anchorage
independent survival in the ascites will result in new approaches to control ovarian cancer associated mortality.
We recently uncovered Sox2, a key developmental gene, as an important regulator of anchorage independent
survival. Sox2’s significance in cancer is underscored by prior reports on Sox2 functions in cancer stem cells
and associations with poor patient survival. Curiously, while close to 75% of ovarian tumors display SOX2 gene
copy number gain, Sox2 expression does not correlate with this SOX2 amplification in tumors. The significance
of SOX2 amplification to the etiology of ovarian cancer progression hence remains elusive. We now find that
Sox2 is significantly elevated in a context-dependent manner in ovarian cancer upon loss of attachment and
necessary for anchorage-independent survival. We have identified a previously unexplored function of Sox2 as
a master regulator of mitochondrial function, an important survival adaptation in anchorage independence. Sox2
promotes mitochondrial respiration and expression of genes required for mitochondrial electron transport chain
transcription and translation, and antioxidant function, including the manganese superoxide dismutase, Sod2.
While Sox2’s most established role is in lineage specification during development, mechanisms by which Sox2
is regulated in ovarian cancer and promotes survival during metastasis are largely unknown. Thus, our objectives
here are to define Sox2 as a convergence point of stress response pathways for mitochondrial control during
ovarian cancer metastasis using a combination of in vitro and in vivo approaches. To accomplish these
objectives, we will: 1) Define regulation of Sox2 under anchorage independence in the context of epigenetic
regulation and metabolic and redox stress associated with loss of attachment; 2) Delineate the mechanisms by
which Sox2 acts as a key regulator of mitochondrial function and quality control; and 3) Determine the necessity
of Sox2-driven mitochondrial function for anchorage independent survival and metastasis. Our studies will
provide significant new knowledge on the dynamic regulation and role of Sox2 in ovarian cancer. Defining the
Sox2-mitochondrial axis as a key adaptation for ovarian cancer anchorage-independent survival and metastasis
will be a major step in identifying key stress adaptations of ovarian cancer that can be targeted therapeutically.

## Key facts

- **NIH application ID:** 10468356
- **Project number:** 7R01CA230628-04
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Nadine Hempel
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $370,349
- **Award type:** 7
- **Project period:** 2021-08-12 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10468356

## Citation

> US National Institutes of Health, RePORTER application 10468356, Role of Sox2 in Stress Adaptations to Ovarian Cancer Anchorage Independence (7R01CA230628-04). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10468356. Licensed CC0.

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