RCAN1.4 suppresses the osteosarcoma growth and metastasis via interfering with the calcineurin/NFAT signaling pathway

Related Experiment Video

Updated: Oct 26, 2025

A Syngeneic Orthotopic Osteosarcoma Sprague Dawley Rat Model with Amputation to Control Metastasis Rate
07:31

A Syngeneic Orthotopic Osteosarcoma Sprague Dawley Rat Model with Amputation to Control Metastasis Rate

Published on: May 3, 2021

3.9K

Bao Huang1,2, Zenghui Jiang1,2, Saishuang Wu1,2

  • 1Department of Orthopedic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, PR China.

Journal of Bone Oncology
|August 2, 2021
PubMed

Insights

Regulator of calcineurin 1 isoform 4 (RCAN1.4) loss promotes osteosarcoma growth and metastasis by increasing calcineurin activity. RCAN1.4 may be a therapeutic target for osteosarcoma.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Calcipressin-1 (RCAN1) regulates calcineurin activity.
  • The role of RCAN1 in osteosarcoma remains unclear.

Purpose of the Study:

  • To investigate the function of RCAN1, specifically RCAN1.4, in osteosarcoma.
  • To determine if RCAN1.4 is a potential therapeutic target for osteosarcoma.

Main Methods:

  • Western blot analysis of RCAN1 protein levels in osteosarcoma and chondroma specimens and cell lines.
  • CRISPR-Cas9 gene editing to create RCAN1.4-deficient osteosarcoma cells.
  • Subcutaneous xenograft and intravenous metastasis models in mice.
  • Analysis of calcineurin activity, NFATc1 nuclear translocation, cyclin D1 and MMPs expression, and osteoclastogenesis.

Main Results:

  • RCAN1 protein levels were lower in osteosarcoma than chondroma specimens.
  • RCAN1.4, not RCAN1.1, was highly expressed in osteosarcoma cell lines.
  • RCAN1.4 deficiency promoted tumor growth, lung metastasis, and osteoclastogenesis.
  • Loss of RCAN1.4 increased calcineurin activity, leading to NFATc1 nuclear translocation and induction of cyclin D1 and MMPs.
  • RCAN1.4 overexpression inhibited osteosarcoma cell growth and invasion.

Conclusions:

  • RCAN1.4 plays a suppressive role in osteosarcoma progression.
  • RCAN1.4 deficiency enhances tumor growth and metastasis via calcineurin/NFATc1 signaling and RANK pathway activation.
  • RCAN1.4 is a potential therapeutic target for osteosarcoma treatment.
Keywords:
CalcineurinNFATOsteoclastOsteosarcomaRCAN1.4

More Related Videos

Development of a Human Preclinical Model of Osteoclastogenesis from Peripheral Blood Monocytes Co-cultured with Breast Cancer Cell Lines06:00

Development of a Human Preclinical Model of Osteoclastogenesis from Peripheral Blood Monocytes Co-cultured with Breast Cancer Cell Lines

Published on: September 13, 2017

7.3K
A RANKL-based Osteoclast Culture Assay of Mouse Bone Marrow to Investigate the Role of mTORC1 in Osteoclast Formation09:37

A RANKL-based Osteoclast Culture Assay of Mouse Bone Marrow to Investigate the Role of mTORC1 in Osteoclast Formation

Published on: March 15, 2018

13.5K

Related Concept Videos

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...
4.0K
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...
4.8K
Canonical Wnt Signaling Pathway02:54

Canonical Wnt Signaling Pathway

The gene encoding the main signaling molecules of the Wnt signaling pathways (the Wnt proteins) was discovered almost four decades ago by Nüsslein-Volhard and Wieschaus. They identified and originally named the gene "wingless" (wg) after a phenotype discovered during their landmark genetic screen in Drosophila for body pattern defects. At around the same time, another researcher named Harold Varmus found that a murine tumor virus activates the mammalian wg homolog, Int-1, which...
9.3K
Non-Canonical Wnt Signaling Pathways01:41

Non-Canonical Wnt Signaling Pathways

Wnt is a zygotic effect gene that is expressed during very early embryonic development. It regulates various processes in animals starting from early development through the adult stage, such as organogenesis in the embryo and maintenance of neuronal and blood stem cells. Wnt proteins can induce a wide variety of intracellular pathways depending upon the specific abilities of different Wnt ligands to form a complex with shared and cognate receptors in the presence of different co-receptors. The...
7.7K
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
5.1K
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...
4.2K