Cellular and molecular mechanisms of plasticity in cancer

Torborg, Stefan R.; Li, Zhuxuan; Chan, Jason E.; Tammela, Tuomas

doi:10.1016/j.trecan.2022.04.007

Cited by 40 publications

(29 citation statements)

References 97 publications

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“…Tumor models. 4T1, MR13, sorted 4T1-Sca-1 + and 4T1-Sca-1 -(5x10 4 Histopathology. Tumors and lungs were harvested at the end of the experiments, fixed in formalin and embedded in paraffin.…”

Section: Methodsmentioning

confidence: 99%

“…Metastasis accounts for over 90% of cancer-related death, calling for new strategies to prevent cancer cell dissemination and metastasis formation (1). Recent studies using single-cell lineage tracing and single-cell RNA sequencing (scRNA-seq) technologies have provided detailed information about intratumor heterogeneity (2, 3), whereby genetically, epigenetically and functionally diverse subpopulations of cancer cells exist within the tumor mass, spatially and temporally (4). Intratumor heterogeneity may arise by modulating cancer cell plasticity, especially of cancer stem cells (CSCs), through cell-intrinsic and - extrinsic mechanisms (5, 6).…”

Section: Introductionmentioning

confidence: 99%

“…In particular, CSCs can acquire metastasis initiating capacities (12) and resistance to therapy, resulting in cancer relapse (4). Moreover, non-CSCs within the tumor bulk may acquire CSC properties to repopulate the tumor(4). While CSC are defined rather functionally by their ability to initiate tumors and metastasis in low number in vivo , several cell surface markers associated with CSC features have been reported, including CD44, CD24, Sca-1, CD61, CD49f were used to identify breast CSCs (13, 14).…”

Section: Introductionmentioning

confidence: 99%

“…Recently, they have been reported to instigate expansion of CSC with metastatic ability (also known as metastasis-initiating cells) in different cancers (17, 23, 24). Thus, the TME dynamics is a key driver of cancer cell plasticity and heterogeneity promoting tumor growth, progression and metastasis (4). Accurate characterization of the regulation of tumor plasticity and heterogeneity by the TME may reveal novel opportunities for developing effective anti-metastatic therapies (8, 14).…”

Section: Introductionmentioning

confidence: 99%

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Tumor-educated Gr1⁺CD11b⁺cells instigate breast cancer metastasis by twisting cancer cells plasticity via OSM/IL6–JAK signaling

Peyvandi¹,

Bulliard²,

Kauzlaric³

et al. 2022

Preprint

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Cancer cell plasticity contributes to tumor therapy resistance and metastasis formation, which represent the main causes of cancer-related death for most cancers, including breast cancer. The tumor microenvironment drives cancer cell plasticity and metastasis and unravelling the underlying cues may provide novel effective strategies to manage metastatic disease. Here we show that stem cell antigen-1 positive (Sca-1+) murine breast cancer cells enriched during tumor progression and metastasis have higherin vitrocancer stem cell-like properties, enhancedin vivometastatic ability, and initiate primary tumors rich in Gr1highCD11b+Ly6Clowcells. In turn, tumor-educated Gr1+CD11b+(Tu-Gr1+CD11b+) cells rapidly and transiently convert low metastatic 4T1-Sca-1-cells into highly metastatic 4T1-Sca-1+cells via secreted OSM and IL6. Moreover, chemotherapy-resistant and highly metastatic 4T1-derived cells maintain high Sca-1+frequency through cell autonomous IL6 production. Inhibition of OSM, IL6 or JAK suppressed Tu-Gr1+CD11b+-induced Sca-1+population enrichmentin vitro, while JAK inhibition abrogated metastasis of chemotherapy-enriched Sca-1+cellsin vivo. Importantly, Tu-Gr1+CD11b+cells invoked a gene signature in tumor cells predicting shorter OS and RFS in breast cancer patients. Collectively, our data identified OSM/IL6-JAK as a clinically relevant paracrine/autocrine axis instigating breast cancer cell plasticity triggering metastasis.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Tumor-educated Gr1⁺CD11b⁺cells instigate breast cancer metastasis by twisting cancer cells plasticity via OSM/IL6–JAK signaling

Peyvandi¹,

Bulliard²,

Kauzlaric³

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…Genetic tracing studies similarly reveal that all such cells are not equally prone to undergo neoplastic and malignant reprogramming ( 12 ). This heterogeneity suggests that for tumorigenesis to proceed, select mutant cells either possess or gain an enhanced ability to acquire novel cell states, a phenomenon known as cellular plasticity ( 13, 14 ).…”

Section: Main Textmentioning

confidence: 99%

Epigenetic plasticity cooperates with emergent cell-cell interactions to drive neoplastic tissue remodeling in the pancreas

Burdziak

Alonso-Curbelo

Walle

et al. 2022

Preprint

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The response to tumor-initiating inflammatory and genetic insults can vary amongst morphologically indistinguishable cells, suggesting yet uncharacterized roles for epigenetic plasticity during early neoplasia. To investigate the origins and impact of such plasticity, we perform single-cell analyses on normal, inflamed, pre-malignant and malignant tissues in autochthonous models of pancreatic cancer. We reproducibly identify heterogeneous cell-states that are primed for diverse late-emerging neoplastic fates and link these to chromatin remodeling at cell-cell communication loci. Using a new inference approach, we reveal signaling gene modules and tissue-level crosstalk, including a neoplasia-driving feedback loop between discrete epithelial and immune cell populations that we validate by genetic perturbation in mice. Our results uncover a neoplasia-specific tissue remodeling program that may be exploited for pancreas cancer interception.

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Unraveling the dangerous duet between cancer cell plasticity and drug resistance

Chatterjee,

Pulipaka,

Subbalakshmi

et al. 2023

Comp Sys Onco

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Cancer cell plasticity is the ability of tumor cells to switch phenotypes and is one of the predominant requisites of cancer cells capable of undergoing metastasis. Cancer cell plasticity is also recognized as one of the major contributors to intratumoral heterogeneity, a critical factor underlying the progression of malignant tumors, which is known to modify tumor response and induce resistance against various modes of therapy, thus posing a barrier to efficient cancer management. Cancer cell plasticity is acquired by the subversion of cell signaling pathways like mitogen‐activated protein kinase pathway, phosphoinositide‐3‐kinase, signal transducer and activator of transcription 3, Wnt, Hedgehog and Notch as well as cellular programs such as epithelial to mesenchymal transition and phenotypic plasticity. This complex phenomenon has been studied in many cancer types like pancreatic cancer, colon cancer and breast cancer. This review will explore the current understanding we have in breast cancer on the intrinsic molecular mechanisms of cancer cell plasticity and the resistance to various types of cancer therapy that arise as a result of plasticity. We conclude by exploring the potential novel therapies that specifically target the pathways leading to plasticity and can be leveraged to treat patients living with the disease.

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Cellular and molecular mechanisms of plasticity in cancer

Cited by 40 publications

References 97 publications

Tumor-educated Gr1⁺CD11b⁺cells instigate breast cancer metastasis by twisting cancer cells plasticity via OSM/IL6–JAK signaling

Tumor-educated Gr1⁺CD11b⁺cells instigate breast cancer metastasis by twisting cancer cells plasticity via OSM/IL6–JAK signaling

Epigenetic plasticity cooperates with emergent cell-cell interactions to drive neoplastic tissue remodeling in the pancreas

Unraveling the dangerous duet between cancer cell plasticity and drug resistance

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Cellular and molecular mechanisms of plasticity in cancer

Cited by 40 publications

References 97 publications

Tumor-educated Gr1+CD11b+cells instigate breast cancer metastasis by twisting cancer cells plasticity via OSM/IL6–JAK signaling

Tumor-educated Gr1+CD11b+cells instigate breast cancer metastasis by twisting cancer cells plasticity via OSM/IL6–JAK signaling

Epigenetic plasticity cooperates with emergent cell-cell interactions to drive neoplastic tissue remodeling in the pancreas

Unraveling the dangerous duet between cancer cell plasticity and drug resistance

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Tumor-educated Gr1⁺CD11b⁺cells instigate breast cancer metastasis by twisting cancer cells plasticity via OSM/IL6–JAK signaling

Tumor-educated Gr1⁺CD11b⁺cells instigate breast cancer metastasis by twisting cancer cells plasticity via OSM/IL6–JAK signaling