Related Experiment Video

Updated: May 12, 2025

Development and Maintenance of a Preclinical Patient Derived Tumor Xenograft Model for the Investigation of Novel Anti-Cancer Therapies
09:29

Development and Maintenance of a Preclinical Patient Derived Tumor Xenograft Model for the Investigation of Novel Anti-Cancer Therapies

Published on: September 30, 2016

13.6K

Colorectal Cancer Cells-Derived Exosomal PIK3CA Mutation DNA Promotes Tumor Metastasis by Activating Fibroblast and

Rui Wang1,2, Wanming Li1, Yuqiong Lv1

  • 1Department of Cell Biology, Key Laboratory of Cell Biology, Ministry of Public Health, Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang, 110122, China.

Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|May 9, 2025
PubMed

Insights

Colorectal cancer (CRC) exosomes carrying PIK3CA mutant DNA activate fibroblasts into cancer-associated fibroblasts (CAFs), promoting metastasis. Detecting exosomal PIK3CA and IL6 may aid CRC diagnosis and treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Metastasis Research

Background:

  • Exosomes mediate tumor metastatic microenvironment (TME) formation via substance delivery.
  • Research on exosomal RNA and proteins is extensive, but exosomal DNA's role remains underexplored.
  • PIK3CA mutations are implicated in various cancers, including colorectal cancer (CRC).

Purpose of the Study:

  • To investigate the role of exosomal PIK3CA mutant DNA in colorectal cancer (CRC) metastasis.
  • To elucidate the mechanism by which exosomal DNA influences the tumor microenvironment.
  • To explore the diagnostic and therapeutic potential of targeting exosomal DNA and related pathways in CRC.

Main Methods:

  • Analysis of colorectal cancer cell-derived exosomes.
  • In vitro co-culture experiments with fibroblasts and exosomes.
  • In vivo metastasis models (e.g., lung metastasis).
  • Detection of PIK3CA mutation in exosomes and cancer-associated fibroblasts (CAFs).
  • Measurement of IL6 levels in CAFs and patient serum.

Main Results:

  • PIK3CAH1047R mutant DNA in CRC exosomes transforms fibroblasts into CAFs by activating the PI3K pathway.
  • CAFs promote tumor cell migration and lung metastasis via elevated IL6 secretion.
  • PIK3CAH1047R mutation is found in CAFs at primary and metastatic sites.
  • CRC patients with PIK3CAH1047R mutation and high IL6 show increased metastasis risk.

Conclusions:

  • Exosomal PIK3CAH1047R DNA drives fibroblast activation and promotes CRC metastasis.
  • Serum exosomal PIK3CA mutation and IL6 levels are potential diagnostic/prognostic biomarkers for CRC metastasis.
  • Targeting PIK3CA mutation and IL6 offers a novel therapeutic strategy for CRC.
Keywords:
cancer‐associated fibroblastscolorectal cancerexosomal PIK3CAH1047R mutation DNAperitumoral microenvironmenttumor metastatic microenvironment

More Related Videos

Molecular Profiling of the Invasive Tumor Microenvironment in a 3-Dimensional Model of Colorectal Cancer Cells and Ex vivo Fibroblasts10:33

Molecular Profiling of the Invasive Tumor Microenvironment in a 3-Dimensional Model of Colorectal Cancer Cells and Ex vivo Fibroblasts

Published on: April 29, 2014

11.0K
Isolation of Circulating Tumor Cells in an Orthotopic Mouse Model of Colorectal Cancer06:19

Isolation of Circulating Tumor Cells in an Orthotopic Mouse Model of Colorectal Cancer

Published on: July 18, 2017

9.9K

Related Concept Videos

Metastasis02:30

Metastasis

Metastasis is the spread of cancer cells from the original site to distant locations in the body. Cancer cells can spread via blood vessels (hematogenous) as well as lymph vessels in the body.
Epithelial-to-Mesenchymal Transition
The epithelial-to-mesenchymal transition or EMT is a developmental process commonly observed in wound healing, embryogenesis, and cancer metastasis. EMT is induced by transforming growth factor-beta (TGF-β) or receptor tyrosine kinase (RTK) ligands, which further...
5.4K
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
Cancer Cell Migration through Invadopodia01:35

Cancer Cell Migration through Invadopodia

Invadosome is a broad category of cell surface structures with proteolytic activity that  degrades the extracellular matrix (ECM). Invadosomes are present in normal cell types, including macrophages, endothelial cells, and neurons, as well as tumor cells. Although the macrophage podosomes and tumor cell invadopodia are classified as invadosomes, they have different structures, molecular pathways, and functions. Podosomes are short structures that last for a few minutes. However,...
2.3K
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...
3.3K
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...
6.1K
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...
4.3K