Related Experiment Video

Updated: Jun 30, 2026

Utilizing Functional Genomics Screening to Identify Potentially Novel Drug Targets in Cancer Cell Spheroid Cultures
07:48

Utilizing Functional Genomics Screening to Identify Potentially Novel Drug Targets in Cancer Cell Spheroid Cultures

Published on: December 26, 2016

Colon carcinoma cells harboring PIK3CA mutations display resistance to growth factor deprivation induced apoptosis

Jing Wang1, Karen Kuropatwinski, Jennie Hauser

  • 1Department of Pharmacology and Therapeutics, Roswell Park Center Institute, Elm and Carlton Streets, Buffalo, NY 14263, USA.

Molecular Cancer Therapeutics
|March 17, 2007
PubMed

Insights

Mutant PIK3CA confers a survival advantage in colon cancer cells under stress by maintaining phosphatidylinositol 3-kinase (PI3K) activity. These cells also show increased dependency on the PI3K pathway for proliferation and survival.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • The PIK3CA gene encodes the p110alpha catalytic subunit of phosphatidylinositol 3-kinase (PI3K).
  • PIK3CA mutations are prevalent in various human cancers, including colon cancer.
  • Understanding the functional consequences of PIK3CA mutations is crucial for cancer therapy.

Purpose of the Study:

  • To investigate the role of PIK3CA mutations in colon cancer cell proliferation and survival under stress.
  • To compare the biological behavior of colon cancer cells with mutant versus wild-type PIK3CA.
  • To determine the dependency of mutant PIK3CA cells on the PI3K pathway.

Main Methods:

  • Screening of colon cancer cell lines for PIK3CA mutations.
  • Comparative analysis of cell proliferation and survival under optimal and stress conditions (growth factor deprivation stress - GFDS).
  • Assessment of PI3K activity, apoptosis induction, DNA synthesis, and PI3K inhibitor sensitivity.
  • Gene silencing using PIK3CA small interfering RNA (siRNA) and ectopic expression of PIK3CA variants.

Main Results:

  • Four out of screened colon cancer cell lines harbored PIK3CA gain-of-function mutations.
  • Mutant PIK3CA cells exhibited constitutive PI3K activity during GFDS, unlike wild-type cells.
  • Mutant cells showed resistance to GFDS-induced apoptosis and hypersensitivity to the PI3K inhibitor LY294002.
  • PIK3CA inhibition via siRNA significantly impacted DNA synthesis and induced apoptosis in mutant cells.
  • Ectopic expression of mutant PIK3CA conferred resistance to GFDS-induced apoptosis.

Conclusions:

  • Mutant PIK3CA enhances colon cancer cell proliferation and survival under environmental stresses like GFDS.
  • Mutant PIK3CA-bearing cells display a heightened dependency on the PI3K pathway for their survival and proliferation.
  • Targeting the PI3K pathway may represent a therapeutic strategy for cancers harboring PIK3CA mutations.

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

Knockdown of FAM83A to Verify Its Role in Cervical Cancer Cell Growth and Cisplatin Sensitivity04:20

Knockdown of FAM83A to Verify Its Role in Cervical Cancer Cell Growth and Cisplatin Sensitivity

Published on: February 9, 2024

Related Concept Videos

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 daughter...
Adaptive Mechanisms in Cancer Cells02:53

Adaptive Mechanisms in Cancer Cells

Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
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...
Cancer-Critical Genes II: Tumor Suppressor Genes01:05

Cancer-Critical Genes II: Tumor Suppressor Genes

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...
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...
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...