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Stress Granule-Associated Protein G3BP2 Regulates Breast Tumor Initiation

Stress Granule-Associated Protein G3BP2 Regulates Breast Tumor Initiation

Nisha Gupta, Mark Badeaux, Yiqian Liu, Kamila Naxerova, Dennis Sgroi, Lance L Munn, Rakesh K Jain, Igor Garkavtsev

Proc Natl Acad Sci U S A. 2017 Jan 31;114(5):1033-1038.

PMID: 28096337

Abstract:

Breast tumors contain tumorigenic cancer cells, termed "tumor-initiating cells" (TICs), which are capable of both replenishing themselves and giving rise to populations of nontumorigenic breast cancer cells (non-TICs). However, the molecular mechanisms responsible for breast tumor initiation remain poorly understood. Here we describe a chemical screening strategy to identify small molecules that enhance the effect of chemotherapeutic agents on TIC-enriched breast cancer cells. We identified proteins that interact with the lead compound C108, including the stress granule-associated protein, GTPase-activating protein (SH3 domain)-binding protein 2, G3BP2. G3BP2 regulates breast tumor initiation through the stabilization of Squamous cell carcinoma antigen recognized by T cells 3 (SART3) mRNA, which leads to increased expression of the pluripotency transcription factors Octamer-binding protein 4 (Oct-4) and Nanog Homeobox (Nanog). Our findings suggest that G3BP2 is important for the process of breast cancer initiation. Furthermore, these data suggest a possible connection between stress granule formation and tumor initiation in breast cancer cells.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP15533092	Compound C108		15533-09-2	Price

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