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Related Concept Videos

The Ras Gene02:38

The Ras Gene

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The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a...
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Abnormal Proliferation02:23

Abnormal Proliferation

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Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
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Cancer-Critical Genes II: Tumor Suppressor Genes01:05

Cancer-Critical Genes II: Tumor Suppressor Genes

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Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
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Loss of Tumor Suppressor Gene Functions01:12

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Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
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Small GTPases - Ras and Rho01:24

Small GTPases - Ras and Rho

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Ras and Rho are small monomeric GTPases that act downstream of receptor tyrosine kinase (RTK) and regulate various cellular processes. These GTPases switch between active and inactive states by binding to guanine nucleotides.
Three regulatory proteins control their activity:
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TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

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The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
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Related Experiment Video

Updated: Oct 3, 2025

Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter
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Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter

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TSPAN6 is a suppressor of Ras-driven cancer.

Patrick O Humbert1, Tamara Zoranovic Pryjda2,3, Blanka Pranjic2

  • 1Department of Biochemistry & Genetics, School of Molecular Sciences, La Trobe University, Bundoora, VIC, 3086, Australia. P.Humbert@latrobe.edu.au.

Oncogene
|February 20, 2022
PubMed
Summary

TSPAN6 acts as a tumor suppressor in RAS-driven cancers. This tetraspanin blocks EGFR signaling, inhibiting tumor growth and metastasis in pancreatic and lung cancers, with low expression predicting poor prognosis.

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In Vivo Inhibition of MicroRNA to Decrease Tumor Growth in Mice
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Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • RAS GTPase mutations drive approximately 30% of human cancers.
  • The tetraspanin Tsp29Fb was identified in a Drosophila screen affecting Ras-driven tumorigenesis.
  • The role of the mammalian orthologue, TSPAN6, in RAS-driven human epithelial tumors remained unknown.

Purpose of the Study:

  • To investigate the function of TSPAN6 in RAS-driven human epithelial cancers.
  • To determine if TSPAN6 acts as a tumor suppressor in pancreatic and lung cancer models.
  • To elucidate the molecular mechanisms by which TSPAN6 affects tumor progression.

Main Methods:

  • Utilized human RAS-activating mutant pancreatic cancer xenografts.
  • Generated whole-body and tumor-cell-specific Tspan6 knockout mouse models.
  • Investigated TSPAN6 binding to EGFR and its effect on EGFR-induced RAS activation.
  • Assessed epithelial-to-mesenchymal transition and cell migration in vitro and in vivo.
  • Correlated TSPAN6 expression with patient prognosis in lung and pancreatic cancers.

Main Results:

  • TSPAN6 suppressed tumor growth and metastasis in human pancreatic cancer xenografts.
  • Tspan6 inactivation in mice enhanced KrasG12D-driven lung tumor initiation and progression.
  • TSPAN6 binds to EGFR, inhibiting EGFR-induced RAS activation.
  • TSPAN6 inactivation promoted epithelial-to-mesenchymal transition and impaired cell migration.
  • Low TSPAN6 expression correlated with poor prognosis in lung and pancreatic cancers with mesenchymal features.

Conclusions:

  • TSPAN6 functions as a novel tumor suppressor receptor in RAS-driven epithelial cancers.
  • TSPAN6 regulates epithelial cell identity and restrains tumor progression.
  • TSPAN6 represents a potential therapeutic target for cancers with RAS mutations.