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The Ras Gene

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 superfamily...

MAPK Signaling Cascades

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...

mTOR Signaling and Cancer Progression

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 Progression

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...

PI3K/mTOR/AKT Signaling Pathway

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...

The Ras Gene

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 superfamily...

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Related Experiment Video

Updated: Jun 22, 2026

Focus Formation: A Cell-based Assay to Determine the Oncogenic Potential of a Gene

Focus Formation: A Cell-based Assay to Determine the Oncogenic Potential of a Gene

Published on: December 31, 2014

Mitochondrial STAT3 supports Ras-dependent oncogenic transformation.

Daniel J Gough¹, Alicia Corlett, Karni Schlessinger

¹Department of Pathology and New York University Cancer Institute, New York University School of Medicine, 550 First Avenue, New York, NY 10016, USA.

Science (New York, N.Y.)

|June 27, 2009

Summary

Signal transducer and activator of transcription 3 (STAT3) supports Ras-driven cancer. STAT3

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Last Updated: Jun 22, 2026

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Transmitochondrial Cybrid Generation Using Cancer Cell Lines

Transmitochondrial Cybrid Generation Using Cancer Cell Lines

Published on: March 17, 2023

Area of Science:

Molecular Biology
Cancer Research
Cell Biology

Background:

Signal transducer and activator of transcription 3 (STAT3) is a transcription factor activated by phosphorylation.
STAT3 typically translocates to the nucleus to regulate gene expression.
Ras oncoproteins are known drivers of malignant transformation.

Purpose of the Study:

To investigate the role of STAT3 in Ras-mediated malignant transformation.
To determine if STAT3's canonical nuclear function is required for Ras transformation.
To explore non-canonical functions of STAT3 in cancer.

Main Methods:

Utilized Ras-transformed cell models.
Employed STAT3 mutants with impaired phosphorylation, nuclear translocation, or DNA binding.
Investigated STAT3 localization using cell biology techniques.
Assessed metabolic changes including glycolysis and oxidative phosphorylation.

Main Results:

Ras-mediated transformation was impaired in the absence of STAT3.
STAT3 mutants lacking canonical functions still supported Ras transformation.
STAT3 was found in mitochondria, independent of nuclear translocation.
Targeting STAT3 exclusively to mitochondria facilitated Ras transformation.
Mitochondrial STAT3 modulated cancer-associated metabolic pathways.

Conclusions:

STAT3 plays a crucial role in Ras-mediated malignant transformation beyond its nuclear transcriptional activity.
STAT3 possesses a non-canonical function within mitochondria that supports cancer metabolism.
Mitochondrial STAT3 directly contributes to the metabolic reprogramming essential for cancer cell survival and proliferation.