SOX9 promotes tumor progression through the axis BMI1-p21CIP
Paula Aldaz1, Maddalen Otaegi-Ugartemendia1, Ander Saenz-Antoñanzas1
1Cellular Oncology Group, Biodonostia Health Research Institute, San Sebastian, Spain.
Scientific Reports
|January 17, 2020
Summary
SOX9 is crucial for cancer cell survival and tumor growth by regulating BMI1 and p21CIP. This study reveals the SOX9-BMI1-p21CIP axis as a key driver of tumor progression in multiple cancers.
Area of Science:
- Oncology
- Molecular Biology
- Developmental Biology
Background:
- SOX9 is a developmental regulator implicated in cancer stem cell (CSC) regulation.
- Its role in differentiated tumor bulk cells remains less understood across various cancers.
Purpose of the Study:
- To investigate SOX9's function in the tumor bulk of gastric cancer, glioblastoma, and pancreatic adenocarcinoma.
- To elucidate the molecular mechanisms underlying SOX9's pro-tumoral activity.
Main Methods:
- SOX9 silencing and gain-of-function studies in vitro and in vivo.
- Analysis of BMI1 and p21CIP expression in response to SOX9 modulation.
- Correlation analysis with clinical cancer samples.
- BMI1 re-establishment experiments.
Main Results:
- SOX9 is essential for cancer cell survival, proliferation, senescence evasion, and tumor growth.
- SOX9 modulates BMI1 and p21CIP expression, with SOX9 levels positively correlating with BMI1 and inversely with p21CIP in clinical samples.
- BMI1 is a critical effector of SOX9's pro-tumoral activity, mediating p21CIP repression.
Conclusions:
- The SOX9-BMI1-p21CIP axis is a significant pathway driving tumor progression in the bulk of gastric cancer, glioblastoma, and pancreatic adenocarcinoma.
- This axis presents potential therapeutic targets for cancer treatment.
More Related Videos
11:13Author Spotlight: Exploring Salidroside's Molecular Mechanisms in Breast Cancer Treatment
Published on: June 9, 2023
2.2K
11:32Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter
Published on: March 27, 2020
7.3K
Related Concept Videos
03:03mTOR Signaling and Cancer Progression
4.5K
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...
The mTOR pathway or the...
4.5K
02:07Tumor Progression
7.1K
Tumor progression is a phenomenon where the pre-formed tumor acquires successive mutations to become clinically more aggressive and malignant. In the 1950s, Foulds first described the stepwise progression of cancer cells through successive stages.
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
7.1K
02:23Abnormal Proliferation
5.0K
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...
5.0K
01:33Pleiotropy
43.1K
Pleiotropy is the phenomenon in which a single gene impacts multiple, seemingly unrelated phenotypic traits. For example, defects in the SOX10 gene cause Waardenburg Syndrome Type 4, or WS4, which can cause defects in pigmentation, hearing impairments, and an absence of intestinal contractions necessary for elimination. This diversity of phenotypes results from the expression pattern of SOX10 in early embryonic and fetal development. SOX10 is found in neural crest cells that form melanocytes,...
43.1K
01:22PI3K/mTOR/AKT Signaling Pathway
5.1K
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...
5.1K
02:17The Tumor Microenvironment
7.5K
Every normal cell or tissue is embedded in a complex local environment called stroma, consisting of different cell types, a basal membrane, and blood vessels. As normal cells mutate and develop into cancer cells, their local environment also changes to allow cancer progression. The tumor microenvironment (TME) consists of a complex cellular matrix of stromal cells and the developing tumor. The cross-talk between cancer cells and surrounding stromal cells is critical to disrupt normal tissue...
7.5K