Related Experiment Video

Updated: May 29, 2026

Initiation of Metastatic Breast Carcinoma by Targeting of the Ductal Epithelium with Adenovirus-Cre: A Novel Transgenic Mouse Model of Breast Cancer
07:13

Initiation of Metastatic Breast Carcinoma by Targeting of the Ductal Epithelium with Adenovirus-Cre: A Novel Transgenic Mouse Model of Breast Cancer

Published on: March 26, 2014

Signalling pathway for RKIP and Let-7 regulates and predicts metastatic breast cancer

Jieun Yun1, Casey A Frankenberger, Wen-Liang Kuo

  • 1Ben May Department for Cancer Research, University of Chicago, IL, USA.

The EMBO Journal
|August 30, 2011
PubMed

Insights

Raf kinase inhibitory protein (RKIP) suppresses breast cancer metastasis by regulating let-7 microRNAs and their targets. This study identifies a novel RKIP-let-7 signaling pathway that predicts metastatic risk.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Tumor metastasis suppressors are crucial in cancer progression, but their mechanisms remain largely unknown.
  • Raf kinase inhibitory protein (RKIP) has been identified as a suppressor of breast tumor metastasis, partly through let-7 microRNA regulation.

Purpose of the Study:

  • To elucidate the downstream signaling pathway of RKIP in inhibiting breast tumor metastasis.
  • To identify novel targets regulated by let-7 within the RKIP pathway.
  • To develop a predictive signature for metastatic risk based on the RKIP signaling cascade.

Main Methods:

  • Integrated analysis of breast tumor gene expression data.
  • Statistical analysis and experimental validation.
  • Investigation of let-7 targets and their role in metastasis-associated gene expression.

Main Results:

  • RKIP inhibits let-7 targets HMGA2 and BACH1, which subsequently upregulate bone metastasis genes (MMP1, OPN, CXCR4).
  • BACH1 is identified as a novel let-7-regulated transcription factor that drives MMP1 expression and promotes metastasis.
  • A novel RKIP pathway metastasis signature (RPMS) accurately predicts high metastatic risk.

Conclusions:

  • The study reveals an integrated RKIP-let-7 signaling pathway critical for regulating breast tumor metastasis.
  • BACH1 emerges as a key mediator in this pathway, linking let-7 regulation to pro-metastatic gene expression.
  • The findings underscore the importance of analyzing gene signaling context for understanding metastasis and developing therapeutic strategies.

More Related Videos

Exploring the Pharmacological Action and Molecular Mechanism of Salidroside in Inhibiting MCF-7 Cell Proliferation and Migration11:13

Exploring the Pharmacological Action and Molecular Mechanism of Salidroside in Inhibiting MCF-7 Cell Proliferation and Migration

Published on: June 9, 2023

Related Concept Videos

mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a rapamycin-insensitive companion...
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
MicroRNAs01:22

MicroRNAs

MicroRNA (miRNA) are short, regulatory RNA transcribed from introns—non-coding regions of a gene—or intergenic regions—stretches of DNA present between genes. Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA ends...