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Circadian Rhythms and Gene Regulation02:19

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The biological clock is involved in many aspects of regulating complex physiology in all animals. It was in 1935 when German zoologists, Hans Kalmus and Erwin Bünning, discovered the existence of circadian rhythm in Drosophila melanogaster. However, the internal molecular mechanisms behind the circadian clock remained a mystery until 1984, when Jeffrey C. Hall, Michael Rosbash, and Michael W. Young discovered the expression of the Per gene oscillating over a 24-hour cycle. In subsequent...
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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.
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Circadian-driven transcriptional programs govern metastatic progression.

Jie Wang1,2, Hao Pan3, Xuan Wang4

  • 1Department of Chinese Medicine & Integrative Medicine, Shanghai Geriatric Medical Center, Zhongshan Hospital, Fudan University, Shanghai 201104, China.

Cancer Biology & Medicine
|April 13, 2026
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Circadian rhythms influence cancer metastasis by regulating the tumor microenvironment (TME). Disrupting these rhythms can promote cancer spread, highlighting chronotherapeutic targets for new cancer treatments.

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Circadian clockTMEcancer therapytumor metastasis

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Area of Science:

  • Oncology
  • Chronobiology
  • Molecular Biology

Background:

  • Circadian rhythms govern 24-hour physiological processes.
  • Circadian disruption is linked to increased cancer risk and progression.
  • The circadian clock influences the tumor microenvironment (TME) and metastasis.

Purpose of the Study:

  • To review mechanisms of circadian regulation within the TME during metastasis.
  • To explore how circadian disruption impacts TME components and metastatic efficiency.
  • To identify chronotherapeutic targets for cancer therapy.

Main Methods:

  • Literature review synthesizing emerging mechanisms.
  • Analysis of data integrating single-cell RNA-seq and intravital imaging.
  • Dissection of how circadian perturbations alter TME networks and responses.

Main Results:

  • Circadian rhythms regulate ECM dynamics, stromal crosstalk, and immune cell extravasation.
  • Circadian disruption alters cytokine networks, hypoxia responses, and metabolic symbiosis in the TME.
  • Emerging data reveal molecular mechanisms underlying circadian control of TME components.

Conclusions:

  • Circadian clock spatiotemporal control is critical for metastatic efficiency.
  • Chronotherapeutic strategies targeting metastasis timing show promise.
  • Further research is needed to fully elucidate molecular mechanisms for novel cancer therapies.