Related Experiment Video

Updated: May 4, 2026

Impedance-based Real-time Measurement of Cancer Cell Migration and Invasion
09:23

Impedance-based Real-time Measurement of Cancer Cell Migration and Invasion

Published on: April 2, 2020

5.8K

CRR9/CLPTM1L regulates cell survival signaling and is required for Ras transformation and lung tumorigenesis

Michael A James1, Haris G Vikis, Everett Tate

  • 1Authors' Affiliation: MCW Cancer Center, Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, Wisconsin.

Cancer Research
|December 25, 2013
PubMed

Insights

The transmembrane protein CLPTM1L promotes non-small cell lung cancer by protecting tumor cells. Blocking CLPTM1L inhibits K-Ras-driven lung tumors, offering potential therapeutic strategies.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Genetics

Background:

  • The transmembrane protein CLPTM1L is overexpressed in non-small cell lung cancer (NSCLC).
  • CLPTM1L contributes to tumor cell survival by inhibiting genotoxic apoptosis.
  • Its role in Ras-driven lung tumorigenesis requires further elucidation.

Purpose of the Study:

  • To investigate the role of CLPTM1L in K-Ras-induced lung tumorigenesis.
  • To elucidate the molecular mechanisms by which CLPTM1L promotes lung cancer.
  • To explore the therapeutic potential of targeting CLPTM1L in NSCLC.

Main Methods:

  • RNA interference (RNAi) was used to block CLPTM1L expression.
  • In vitro assays assessed morphologic transformation, anchorage-independent growth, and anoikis survival.
  • Mechanistic studies involved investigating interactions with phosphoinositide 3-kinase (PI3K) and assessing AKT phosphorylation and Bcl-xL regulation.

Main Results:

  • RNAi-mediated blockade of CLPTM1L inhibited K-Ras-induced lung tumorigenesis.
  • CLPTM1L was essential for Ras-induced morphologic transformation, anchorage-independent growth, and anoikis survival.
  • CLPTM1L interacts with PI3K, is crucial for Ras-induced AKT phosphorylation, and regulates the anti-apoptotic protein Bcl-xL independently of AKT.
  • Constitutive activation of AKT or Bcl-xL rescued the transformed phenotype in CLPTM1L-depleted cells.
  • The CLPTM1L gene locus (5p15.33) is associated with lung cancer risk, with risk genotypes correlating to higher CLPTM1L expression.

Conclusions:

  • CLPTM1L plays a critical protumorigenic role in Ras-driven lung cancers.
  • CLPTM1L's function is essential for key oncogenic processes including transformation and survival.
  • Targeting CLPTM1L may offer a therapeutic strategy for NSCLC and enhance chemosensitization.

More Related Videos

The Soft Agar Colony Formation Assay08:01

The Soft Agar Colony Formation Assay

Published on: October 27, 2014

112.5K
Detection of Mitochondria Membrane Potential to Study CLIC4 Knockdown-induced HN4 Cell Apoptosis In Vitro13:20

Detection of Mitochondria Membrane Potential to Study CLIC4 Knockdown-induced HN4 Cell Apoptosis In Vitro

Published on: July 17, 2018

9.9K

Related Concept Videos

The Ras Gene02:38

The Ras Gene

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...
5.7K
Abnormal Proliferation02:23

Abnormal Proliferation

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...
4.0K
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...
3.6K
Small GTPases - Ras and Rho01:24

Small GTPases - Ras and Rho

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:
4.4K
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...
7.3K
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...
5.1K