TRPV3 inhibits colorectal cancer cell proliferation and migration by regulating the MAPK signaling pathway

Wei Yu1, Jieping Huang2, Hui Yu1

  • 1Department of Clinical Pharmacy, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, China.

Abstract

Insights

Low expression of transient receptor potential vanilloid 3 (TRPV3) in colorectal cancer (CRC) is linked to poor prognosis. TRPV3 inhibits cancer cell proliferation and migration by suppressing the MAPK signaling pathway.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Transient receptor potential vanilloid 3 (TRPV3) is a potential target in cancer therapy.
  • Colorectal cancer (CRC) is a significant global health concern with a need for improved prognostic markers.
  • Understanding the role of TRPV3 in CRC progression is crucial for developing novel treatment strategies.

Purpose of the Study:

  • To investigate the inhibitory effect of TRPV3 on colorectal cancer (CRC) cell proliferation and migration.
  • To explore the underlying molecular mechanisms, including signaling pathways involved.
  • To evaluate the prognostic value of TRPV3 expression in CRC patients.

Main Methods:

  • Analysis of a large microarray dataset (GSE39582) and validation using 100 CRC tissue samples.
  • In vitro functional assays: Cell Counting Kit-8 (CCK-8) for proliferation and Transwell assay for migration.
  • Gene Set Enrichment Analysis (GSEA) to identify regulated pathways, including the mitogen-activated protein kinase (MAPK) pathway.
  • In vivo experiments to confirm the role of TRPV3 and MAPK signaling.

Main Results:

  • Low TRPV3 expression is significantly associated with poor prognosis in CRC patients, validated at both gene and protein levels.
  • TRPV3 knockdown enhanced CRC cell proliferation and migration, while TRPV3 overexpression inhibited these processes.
  • TRPV3 silencing promoted CRC cell proliferation and migration by activating the MAPK signaling pathway.

Conclusions:

  • Low TRPV3 expression indicates a poor prognosis in colorectal cancer patients.
  • TRPV3 acts as an inhibitor of CRC cell proliferation and migration.
  • The mechanism involves the suppression of the MAPK signaling pathway by TRPV3.

Related Concept Videos

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...
5.9K
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...
6.4K
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...
3.9K
Tumor Progression02:07

Tumor Progression

Tumor progression is a phenomenon where the pre-formed tumor acquires successive mutations to become clinically more aggressive and malignant. In the 1950s, Foulds first described the stepwise progression of cancer cells through successive stages.
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
6.4K
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...
3.8K
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,...
2.4K