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RETRACTED: Insulin-Induced Gene 2 Expression Is Associated with Breast Cancer Metastasis
1Department of Breast Medical Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Ministry of Education, Tianjin, China.
The American Journal of Pathology
|December 15, 2020
Summary
Insulin-induced gene 2 (INSIG2) plays a role in breast cancer progression and metastasis. Higher INSIG2 expression is linked to poorer survival, particularly in Asian patients.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Insulin-induced gene 2 (INSIG2) inhibits cholesterol biosynthesis and is implicated in colon and pancreatic cancers.
- Cholesterol is a known risk factor for breast cancer, but its precise role and regulatory mechanisms remain unclear.
- Understanding INSIG2's function in breast cancer is crucial for identifying new therapeutic targets.
Purpose of the Study:
- To investigate the role of INSIG2 in breast cancer development and progression.
- To correlate INSIG2 expression with breast cancer subtypes, metastatic potential, and patient survival.
Main Methods:
- Correlation of INSIG2 mRNA and protein expression with metastatic potential in breast cancer cell lines.
- In vitro knockdown and overexpression studies of INSIG2 to assess effects on epithelial-to-mesenchymal transition (EMT), proliferation, and metabolism.
- In vivo experimental metastasis assays.
- Analysis of INSIG2 protein expression in breast cancer tissue microarrays.
- Examination of INSIG2 mRNA expression and survival data from The Cancer Genome Atlas (TCGA).
Main Results:
- INSIG2 knockdown inhibited EMT, while overexpression induced it.
- INSIG2 knockdown altered cellular metabolism in vitro and reduced experimental metastasis in vivo, without affecting proliferation.
- Higher INSIG2 protein expression was observed in breast cancer tissues and correlated with triple-negative and HER2+ subtypes.
- TCGA data showed lower INSIG2 mRNA in triple-negative breast cancer, contrasting with protein expression.
- Elevated INSIG2 mRNA correlated with poorer survival, especially in Asian patients.
Conclusions:
- INSIG2 has a significant, previously undefined role in breast cancer pathophysiology, influencing EMT, metabolism, and metastasis.
- INSIG2 expression patterns differ between mRNA and protein levels and across molecular subtypes.
- INSIG2 may represent a prognostic biomarker, particularly for breast cancer patients in Asia.
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