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Updated: Jan 18, 2026
Isolation and Functional Assessment of Human Breast Cancer Stem Cells from Cell and Tissue Samples
Published on: October 2, 2020
Sparking malignancy: nicotine as a driver of stemness and metastasis in triple-negative breast cancer†
Christopher Simpkins1, Eneda Toska1,2
1Sidney Kimmel Comprehensive Cancer Center and Department of Oncology, Johns Hopkins University, Baltimore, MD, USA.
Abstract:
Triple-negative breast cancer (TNBC) lacks expression of estrogen receptor (ER), progesterone receptor (PR), and HER2, and remains one of the most aggressive and therapeutically challenging breast cancer subtypes, marked by early relapse, metastasis, and limited targeted treatment options. In a recent study published in The Journal of Pathology, Kuo et al provide compelling evidence that nicotine exposure, whether from tobacco smoke or e-cigarette vapor, drives TNBC progression by promoting stem-like and metastatic phenotypes. Integrating clinical datasets, patient tissues, cell lines, and in vivo models, the authors demonstrate that nicotine enhances tumor aggressiveness via coordinated upregulation of CHRNA9 and IGF1R. Silencing either receptor attenuates nicotine-induced stemness, invasion, and metastasis, revealing a therapeutically actionable axis. High expression of CHRNA9 and IGF1R correlates with poor clinical outcomes and may define a nicotine-exposed TNBC subgroup that could benefit from IGF1R-targeted therapy or repurposed nicotinic receptor antagonists. These findings underscore the role of environmental exposures in shaping tumor biology and offer a mechanistic basis for the poorer prognosis observed in smokers with breast cancer. © 2025 The Pathological Society of Great Britain and Ireland.
Insights
Nicotine exposure, from smoking or vaping, fuels aggressive triple-negative breast cancer (TNBC) by increasing stem-like and metastatic traits. Targeting CHRNA9 and IGF1R may offer new therapeutic strategies for this challenging cancer.
Area of Science:
- Oncology
- Molecular Biology
- Environmental Health
Background:
- Triple-negative breast cancer (TNBC) is aggressive, lacking ER, PR, and HER2 expression, leading to poor prognosis and limited treatment options.
- Environmental factors like nicotine exposure are increasingly recognized for their role in cancer progression.
Purpose of the Study:
- To investigate the impact of nicotine exposure on TNBC progression.
- To identify molecular mechanisms driving nicotine-induced tumor aggressiveness and metastasis.
- To explore potential therapeutic targets within the nicotine-signaling pathway.
Main Methods:
- Integration of clinical datasets and patient tissues with in vitro cell line and in vivo animal models.
- Analysis of gene expression changes, specifically focusing on CHRNA9 and IGF1R.
- Functional studies involving receptor silencing to assess effects on cancer phenotypes.
Main Results:
- Nicotine exposure promotes stem-like and metastatic phenotypes in TNBC.
- Nicotine upregulates CHRNA9 and IGF1R, enhancing tumor aggressiveness, invasion, and metastasis.
- Silencing CHRNA9 or IGF1R significantly attenuates nicotine-driven TNBC progression.
- High CHRNA9 and IGF1R expression correlates with poor clinical outcomes in TNBC patients.
Conclusions:
- Nicotine exposure drives TNBC progression through the CHRNA9 and IGF1R axis.
- This axis represents a potential therapeutic target for nicotine-exposed TNBC.
- Findings highlight the impact of environmental exposures on breast cancer biology and prognosis.
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