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Updated: Mar 8, 2026

Induction and Analysis of Epithelial to Mesenchymal Transition
Published on: August 27, 2013
ERK2-ZEB1-miR-101-1 axis contributes to epithelial-mesenchymal transition and cell migration in cancer
Kailash Chandra Mangalhara1, Siddharth Manvati2, Sunil Kumar Saini1
1School of Life Sciences, Jawaharlal Nehru University, New Delhi, Delhi 110067, India.
Abstract:
Regulation of metastasis continues to remain enigmatic despite our improved understanding of cancer. Identification of microRNAs associated with metastasis in the recent past has provided a new hope. Here, we show how microRNA-101 (miR-101) regulates two independent processes of cellular metastasis by targeting pro-metastatic upstream regulatory transcription factors, ZEB1 and ZEB2, and downstream effector-actin modulators, RHOA and RAC1, providing a single target for therapeutic intervention. Further, we depict how down-regulation of miR-101 by extracellular signal-regulated kinase-2 (ERK2) is vital for MAP kinase pathway induced cellular migration and mesenchymal transition. Importantly, EKR2 induced expression of ZEB1 seems essential for down-regulation of miR-101-1 and induction of EMT. Given the role of EMT in metastasis, we also observe a significant correlation between miR-101 expression and lymph node metastasis; and identify the ERK2-ZEB1-miR-101-1 pathway active in breast cancer tissues, with an apparent clinicopathological implication.
Insights
MicroRNA-101 (miR-101) targets key factors regulating cancer metastasis. This microRNA, controlled by ERK2, offers a potential therapeutic target for reducing tumor spread and improving patient outcomes.
Area of Science:
- Molecular Biology
- Oncology
- Biochemistry
Background:
- Cancer metastasis remains a complex challenge despite advances in cancer research.
- MicroRNAs have emerged as critical regulators of cellular processes, including metastasis.
Purpose of the Study:
- To elucidate the role of microRNA-101 (miR-101) in regulating cellular metastasis.
- To identify the molecular mechanisms underlying miR-101's function in metastasis and its potential as a therapeutic target.
Main Methods:
- Investigated miR-101's targeting of transcription factors (ZEB1, ZEB2) and actin modulators (RHOA, RAC1).
- Examined the regulation of miR-101 by extracellular signal-regulated kinase-2 (ERK2) and its impact on the MAP kinase pathway.
- Assessed the correlation between miR-101 expression and lymph node metastasis in breast cancer tissues.
Main Results:
- miR-101 directly targets ZEB1, ZEB2, RHOA, and RAC1, inhibiting key metastatic processes.
- ERK2 down-regulates miR-101, promoting cellular migration and epithelial-mesenchymal transition (EMT).
- A significant correlation was observed between reduced miR-101 expression and lymph node metastasis in breast cancer.
Conclusions:
- miR-101 is a crucial regulator of cancer metastasis by targeting multiple pro-metastatic factors.
- The ERK2-ZEB1-miR-101 pathway is implicated in breast cancer metastasis and holds potential for therapeutic intervention.
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