Cancer cells adapting in a hostile environment

Cancer's Secret Weapon: How Metastatic Cells Adapt and Thrive

Beau Callahan in Health & Wellness December 2025 • 4 min read.

"Unlocking the mysteries of how cancer cells survive in hostile environments could revolutionize treatment strategies."

Cancer metastasis is the primary cause of cancer-related deaths, with its complex processes remaining the least understood aspect of cancer biology. One key factor in cancer cell survival and spread is metabolic reprogramming—the ability of cancer cells to alter their energy production methods to thrive even when nutrients are scarce, such as within solid tumors. Understanding how metastatic cells differ from primary tumor cells in their bioenergetic adaptations is critical for developing effective treatments.

A recent study published in the International Journal of Oncology sheds light on these differences by comparing primary tumor cells and metastatic tumor cells in unfavorable microenvironments. Researchers Yunlong Cheng, Yusheng Lu, and colleagues discovered that metastatic cells exhibit a stronger bioenergetic adaptation than primary tumor-derived cells. This adaptation involves sustained elevation of glycolysis, a process that allows cells to produce energy without oxygen, and careful regulation of the cell cycle to conserve energy when needed.

This research provides valuable insights into how metastatic cancer cells survive and thrive, potentially paving the way for new therapeutic strategies that target their unique metabolic vulnerabilities.

Decoding the Metabolic Makeover: How Cancer Cells Thrive in Harsh Conditions

Cancer cells adapting in a hostile environment

Metastatic cancer cells exhibit remarkable metabolic flexibility, allowing them to survive and proliferate even when faced with limited nutrients and oxygen. This adaptation involves several key processes:

Increased Glycolysis: Metastatic cells rely heavily on glycolysis, a process that converts glucose into energy without using oxygen. This allows them to thrive in oxygen-poor environments often found within tumors. This remarkable glycolytic ability is associated with high expression levels of key enzymes like hexokinase (HK)1 and HK2, glucose transporter type 1 (GLUT1), and hypoxia-inducible factor 1a (HIF-1a).

Hexokinase (HK)1 and HK2: These enzymes are crucial for the first step of glycolysis, the process of phosphorylating glucose. Higher levels of these enzymes mean that cancer cells can rapidly process glucose for energy.
Glucose Transporter Type 1 (GLUT1): This protein helps transport glucose across the cell membrane, ensuring a steady supply of fuel for glycolysis.
Hypoxia-Inducible Factor 1a (HIF-1a): This transcription factor activates genes involved in glycolysis and other metabolic processes that help cells survive in low-oxygen conditions.

Cell Cycle Regulation: Metastatic cells carefully regulate their cell cycle to conserve energy. When energy is scarce, they inhibit the expression of cell cycle regulatory proteins, effectively pausing cell division to prioritize survival.Mesenchymal Transition and Stem Cell Characteristics: Metastatic cells often undergo a process called epithelial-mesenchymal transition (EMT), which gives them properties that promote migration and invasion. They also exhibit stem cell characteristics, which contribute to their ability to self-renew and form new tumors. SW620 cells, for example, highly expressed CD133 and CD166, markers associated with stem cells, which were absent in SW480 cells.

The Road Ahead: Targeting Metabolic Pathways for Cancer Therapy

By understanding how metastatic cancer cells adapt their metabolism to survive in challenging conditions, researchers can develop new therapies that specifically target these adaptations. For example, drugs that inhibit glycolysis or disrupt the cell cycle in metastatic cells could potentially prevent or slow down the spread of cancer. This study provides a promising starting point for future research aimed at developing more effective cancer treatments.

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This article was crafted using a human-AI hybrid and collaborative approach. AI assisted our team with initial drafting, research insights, identifying key questions, and image generation. Our human editors guided topic selection, defined the angle, structured the content, ensured factual accuracy and relevance, refined the tone, and conducted thorough editing to deliver helpful, high-quality information.See our About page for more information.

This article is based on research published under:

DOI-LINK: 10.3892/ijo.2018.4582, Alternate LINK

Title: Metastatic Cancer Cells Compensate For Low Energy Supplies In Hostile Microenvironments With Bioenergetic Adaptation And Metabolic Reprogramming

Subject: Cancer Research

Journal: International Journal of Oncology

Publisher: Spandidos Publications

Authors: Yunlong Cheng, Yusheng Lu, Doudou Zhang, Shu Lian, Haiyan Liang, Yuying Ye, Ruizhi Xie, Shuhui Li, Jiahang Chen, Xuhui Xue, Jingjing Xie, Lee Jia

Published: 2018-10-02

Everything You Need To Know

What is the key factor that allows metastatic cancer cells to survive and spread, and why is it important?

Metastatic cancer cells' survival and spread hinges on their metabolic reprogramming, the ability to modify their energy production. This allows them to thrive in nutrient-scarce environments, like those within solid tumors. Unlike primary tumor cells, the metastatic cells have a stronger adaptation, especially through elevated glycolysis, which helps them produce energy without oxygen. The implications of this involve these cells' ability to maintain their energy needs to keep going and spreading the cancer.

What is Glycolysis, and how does it help metastatic cancer cells?

Glycolysis is a crucial process where metastatic cancer cells convert glucose into energy without oxygen. This process is essential for survival in oxygen-poor environments. The elevated activity of Glycolysis is linked to higher expression of Hexokinase (HK)1 and HK2, Glucose Transporter Type 1 (GLUT1), and Hypoxia-Inducible Factor 1a (HIF-1a), which work together to ensure a steady supply of glucose and support the metabolic demands. Understanding this process offers potential therapeutic targets to disrupt the energy supply of metastatic cells and prevent cancer spread.

How do Hexokinase (HK)1, HK2, Glucose Transporter Type 1 (GLUT1), and Hypoxia-Inducible Factor 1a (HIF-1a) help cancer cells?

Hexokinase (HK)1 and HK2 are key enzymes that drive the first step of glycolysis, the process of phosphorylating glucose. Higher levels in metastatic cells allow for rapid energy production from glucose. Glucose Transporter Type 1 (GLUT1) is a protein that helps transport glucose into the cell, ensuring a constant supply of fuel for glycolysis. Hypoxia-Inducible Factor 1a (HIF-1a) is a transcription factor that activates genes involved in glycolysis, allowing the cell to adapt to low-oxygen environments. All of these work together to make energy.

How do metastatic cancer cells regulate their cell cycle, and what other characteristics aid their survival?

Metastatic cells carefully manage their cell cycle to conserve energy, which is another way that they are able to survive. When energy is limited, these cells will pause cell division by inhibiting the expression of cell cycle regulatory proteins to prioritize survival. Mesenchymal transition (EMT) gives cells properties to help with migration and invasion. Stem cell characteristics help with self-renewal and formation of new tumors. SW620 cells have CD133 and CD166, which are markers associated with stem cells. SW480 cells don't have those markers.

How can understanding the metabolic processes of metastatic cancer cells lead to new treatments?

By focusing on the unique metabolic adaptations of metastatic cancer cells, researchers aim to develop targeted therapies. The identification of the enhanced glycolysis in these cells reveals potential vulnerabilities. Drugs that inhibit glycolysis or disrupt the cell cycle in metastatic cells could limit cancer's spread. This study provides a foundation for further research into more effective treatments for cancer, particularly those that prevent or slow metastasis.