Related Experiment Video

Updated: Feb 23, 2026

Quantitative PCR-based Assay to Measure Sonic Hedgehog Signaling in Cellular Model of Ciliogenesis
07:26

Quantitative PCR-based Assay to Measure Sonic Hedgehog Signaling in Cellular Model of Ciliogenesis

Published on: January 31, 2025

1.1K

Hedgehog Inhibition Upregulates TRK Expression to Antagonize Tumor Suppression in Small Cell Lung Cancer Cells

Hideya Onishi1, Katsuya Nakamura2, Shuntaro Nagai3

  • 1Departments of Cancer Therapy and Research, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan ohnishi@surg1.med.kyushu-u.ac.jp.

Anticancer Research
|September 6, 2017
PubMed
Abstract

Insights

Negative crosstalk between tropomyosin-related kinase B (TRKB) and Hedgehog (Hh) signaling pathways was detected in small cell lung cancer (SCLC). Combined inhibition of TRKB and Hh pathways may offer a novel treatment strategy for refractory SCLC.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Signaling Pathways

Background:

  • Tropomyosin-related kinase B (TRKB) and Hedgehog (Hh) signaling pathways are implicated in cancer malignancy.
  • Previous clinical trials with TRK and Hh inhibitors in small cell lung cancer (SCLC) showed disappointing results.
  • Potential crosstalk between TRKB and Hh signaling pathways may explain treatment resistance.

Purpose of the Study:

  • To investigate the crosstalk between TRKB and Hh-GLI1 signaling pathways in SCLC.
  • To determine the contribution of TRKB and Hh signaling to proliferation and invasiveness in SBC-5 cells.

Main Methods:

  • Utilized the human small cell lung carcinoma cell line, SBC-5.
  • Employed small interfering RNA (siRNA) to inhibit TRKB and Hh signaling.
  • Assessed proliferation, migration, and invasiveness following gene knockdown.

Main Results:

  • Hedgehog (Hh)-GLI1 knockdown alone did not impact SBC-5 cell invasiveness.
  • TRKB expression increased in GLI1 siRNA-transfected cells.
  • Combined knockdown of TRKB and GLI1 significantly reduced invasiveness, proliferation, and migration.

Conclusions:

  • Hh inhibition appears to upregulate TRKB expression, potentially as a compensatory mechanism against tumor suppression.
  • The findings suggest that targeting both TRKB and Hh pathways concurrently could be a promising therapeutic approach for SCLC.
  • Combined TRKB and Hh inhibition demonstrated superior efficacy in reducing cancer cell proliferation and invasiveness compared to single-agent inhibition.
Keywords:
Hedgehog signalSBC-5TrkB signalsmall cell lung cancer

More Related Videos

Monitoring Hippo Signaling Pathway Activity Using a Luciferase-based Large Tumor Suppressor LATS Biosensor07:16

Monitoring Hippo Signaling Pathway Activity Using a Luciferase-based Large Tumor Suppressor LATS Biosensor

Published on: September 13, 2018

20.8K
Cell Population Analyses During Skin Carcinogenesis06:53

Cell Population Analyses During Skin Carcinogenesis

Published on: August 21, 2013

13.0K

Related Concept Videos

Hedgehog Signaling Pathway02:33

Hedgehog Signaling Pathway

The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...
10.2K
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...
7.4K
Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR...
2.9K
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...
4.9K
Enzyme-linked Receptors01:00

Enzyme-linked Receptors

Enzyme-linked receptors are proteins that act as both receptor and enzyme, activating multiple intracellular signals. This is a large group of receptors that include the receptor tyrosine kinase (RTK) family. Many growth factors and hormones bind to and activate the RTKs.
Neurotrophin (NT) receptors are a family of RTKs, including trkA, trkB, and trkC (tropomyosin-related kinase) receptors. TrkA is specific for nerve growth factor (NGF), neurotrophin-6, and neurotrophin-7. TrkB binds...
87.2K
Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
8.2K