Related Experiment Video

Updated: Aug 25, 2026

Tropomodulin 3 Overexpression as a Marker for Platinum Resistance and Immune Infiltration in Ovarian Cancer
09:40

Tropomodulin 3 Overexpression as a Marker for Platinum Resistance and Immune Infiltration in Ovarian Cancer

Published on: August 2, 2024

Modulation of Janus kinase 2 by cisplatin in cancer cells

Hui Song1, Vernon K Sondak, Dwayne L Barber

  • 1Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Michigan Comprehensive Cancer Center, Ann Arbor, MI 48109-0936, USA.

International Journal of Oncology
|March 11, 2004
PubMed

Insights

Cisplatin effectively inhibits the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway in cancer cells. This chemotherapy agent reduces cancer cell growth and survival by de-phosphorylating key JAK/STAT proteins.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Constitutive activation of Janus kinases (JAKs) and signal transducers and activators of transcription (STATs) is common in human cancers.
  • The JAK/STAT pathway plays a critical role in cancer cell proliferation and survival.
  • Targeting the JAK/STAT pathway is a potential therapeutic strategy for cancer treatment.

Purpose of the Study:

  • To investigate the effect of the chemotherapeutic agent cisplatin on the JAK/STAT pathway in cancer cells.
  • To determine if cisplatin can inhibit the activity and phosphorylation of JAKs and STATs.
  • To elucidate the mechanism by which cisplatin affects the JAK/STAT pathway.

Main Methods:

  • Treatment of ovarian cancer, sarcoma, and leukemia cells with cisplatin.
  • Assessment of JAK2, TEL-JAK2, and STAT3 tyrosine phosphorylation and kinase activity.
  • Analysis of anti-apoptotic protein BcL-XL levels.
  • Investigation of the role of tyrosine phosphatase SHP-1 and SOCS family members.

Main Results:

  • Cisplatin significantly inhibited JAK2 tyrosine phosphorylation and kinase activity in ovarian cancer and sarcoma cells in a dose- and time-dependent manner.
  • Cisplatin reduced STAT3 tyrosine phosphorylation and down-regulated the anti-apoptotic protein BcL-XL.
  • In leukemia cells, cisplatin markedly inhibited TEL-JAK2 tyrosine phosphorylation.
  • Cisplatin's down-regulation of JAK2 appeared to involve modulation of SHP-1, not SOCS family members.

Conclusions:

  • Cisplatin effectively down-regulates the JAK/STAT signaling pathway in various cancer cells.
  • The mechanism involves the de-phosphorylation of JAK/STAT proteins.
  • Cisplatin's inhibition of the JAK/STAT pathway may contribute to its anti-cancer effects.

More Related Videos

Evaluating the Effectiveness of Cancer Drug Sensitization In Vitro and In Vivo09:19

Evaluating the Effectiveness of Cancer Drug Sensitization In Vitro and In Vivo

Published on: February 6, 2015

Related Concept Videos

The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
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...
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...
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...
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...
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...