Chitosan promotes cancer progression and stem cell properties in association with Wnt signaling in colon and hepatocellular carcinoma cells

Chang, Pen-Heng; Sekine, Keisuke; Chao, Hsiao-Mei; Hsu, Shan‐hui; Chern, Edward

doi:10.1038/srep45751

Cited by 45 publications

(33 citation statements)

References 61 publications

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“…Cancer stem cells play a pivotal role in invasion, metastasis, and chemotherapy resistance . The expression of CD133 and CD44 are indicators of cancer cell stemness . To evaluate the regulation of stemness by KAP1 in NSCLC, we compared sphere formation in KAP1 −/− and WT A549 cells.…”

Section: Resultsmentioning

confidence: 99%

KAP1 inhibits the Raf‐MEK‐ERK pathway to promote tumorigenesis in A549 lung cancer cells

Pen

Huang

et al. 2018

Molecular Carcinogenesis

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Aberrant activation of the Raf-MEK-ERK pathway has frequently been associated with various cancers, especially lung cancer. However, the key regulators of this pathway are largely unknown. Using functional proteomics screening, we found that KAP1 interacts with c-Raf. Knocking out KAP1 decreased c-Raf phosphorylation at serine 259 and increased its phosphorylation at serine 338, which activated MEK and ERK. We detected higher KAP1 expression in lung cancer tissues than in normal peri-tumoral tissues. KAP1 knockdown arrested A549 lung cancer cells in the G0/G1 phase of the cell cycle and attenuated cell growth, metastasis, the epithelial-mesenchymal transition, angiogenesis, stemness, and colony formation. Furthermore, knocking out KAP1 remarkably increased the susceptibility of A549 cells to the anti-cancer drug 5-Fluorouracil, which correlated with increasing ERK phosphorylation. In vivo xenograft experiments suggested that KAP1 deficiency significantly decreases the tumorigenicity of A549 cells. Taken together, our findings indicate that KAP1 acts as a key module in the c-Raf-interactome complex and regulates lung cancer development through the Raf-MEK-ERK pathway. Therefore, KAP1 may represent a potential diagnosis biomarker and new treatment target for lung cancer.

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Section: Resultsmentioning

confidence: 99%

KAP1 inhibits the Raf‐MEK‐ERK pathway to promote tumorigenesis in A549 lung cancer cells

Pen

Huang

et al. 2018

Molecular Carcinogenesis

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“…Previous studies have reported CSCs to be involved in the stepwise progression of solid tumors including breast, gastric, and cervical cancer . CD44 and activation of WNT, NOTCH1 increases aggressiveness, correlating with progression in colon cancer . CD133 is also associated with enrichment of undifferentiated cells and tumorigenic behavior along with its implication in epithelial dedifferentiation .…”

Section: Discussionmentioning

confidence: 99%

Cancer stem cells and fibroblast niche cross talk in an in‐vitro oral dysplasia model

Kulsum

Raju²,

Raghavan³

et al. 2019

Molecular Carcinogenesis

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Understanding the cellular interactions during oral carcinogenesis has the potential to identify novel prognostic and therapeutic targets. This study aimed at investigating the cancer stem cell (CSC)‐fibroblast niche interactions using in‐vitro dysplastic cell line models developed from different stages of 4NQO‐induced oral carcinogenic mice model. The spontaneously transformed epithelial cells (DysMSCTR6, 14 and 16) were developed from three time points (mild/moderate/severe), while two fibroblast cell lines (FibroMSCTR12, 16) were developed from moderate and severe dysplastic tissue. The epithelial (Epcam+/Ck+) and the fibroblast cell lines (Vimentin+/α‐SMA+/Ck‐) were authenticated and assessment of cells representing progressive grades of dysplastic severity indicated a significant increase in dysplastic marker profile (P < 0.05). Evaluation of the CSC characteristics showed that an increase in expression of Cd133, Cd44, Aldh1a1, Notch1, and Sox2 was accompanied by an increase in migratory (P > 0.05) and colony formation capacity (P > 0.005). Targeting Notch1 (GSI inhibitor PZ0187; 30 μM), showed a significant reduction in cell proliferation capacity (P < 0.05) and in the dysplastic marker profile. Further, Notch1 inhibition resulted in down regulation of Cd133 and Aldh1a 1 (P < 0.05) and a complete abrogation of colony formation ability (P < 0.0001). The effect of niche interactions evaluated using FibroMSCTR12‐conditioned media studies, revealed an enrichment of ALDH1A1+ cells (P < 0.05), induction of spheroid formation ability (P < 0.0001) and increased proliferation capacity (3.7 fold; P < 0.005). Although PZ0187 reduced cell viability by ∼40%, was unable to abrogate the conditioned‐media induced increase in proliferation capacity completely. This study reports a Notch‐1 dependent enrichment of CSC properties during dysplastic progression and a Notch‐1 independent dysplastic cell‐fibroblast interaction during oral carcinogenesis.

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“…Currently, there is a large number of studies concerning the applications of chitosan in cancer therapy. For instance, it is reported that culturing colon and hepatocellular carcinoma cells on chitosan results in enhanced motility, the capacity of self‐renewal, and drug resistance . Moreover, chitosan can probably initiate the canonical Wnt/β‐catenin‐CD44 axis signaling in colon cancer, as well as Wnt‐STAT3 signaling in hepatocellular carcinoma .…”

Section: Chitosan Roles In Diagnosis and Treatment Of Cancersmentioning

confidence: 99%

“…For instance, it is reported that culturing colon and hepatocellular carcinoma cells on chitosan results in enhanced motility, the capacity of self‐renewal, and drug resistance . Moreover, chitosan can probably initiate the canonical Wnt/β‐catenin‐CD44 axis signaling in colon cancer, as well as Wnt‐STAT3 signaling in hepatocellular carcinoma . Chitosan and its NPs have shown antiproliferative effects on breast cancer cell lines, including MDA‐MB‐231 and SK‐BR‐3 .…”

Section: Chitosan Roles In Diagnosis and Treatment Of Cancersmentioning

confidence: 99%

Chitosan is a potential inhibitor of ovarian cancer: Molecular aspects

et al. 2019

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Although ovarian cancer has a lower prevalence than breast cancer, its mortality rate is three times higher, which is reported to increase in the coming years. As the early stages of ovarian cancer do not have any obvious symptoms, in most of the cases, this cancer is diagnosed at advanced stages with a poor prognosis. Moreover, in many patients who are diagnosed with advanced stage, relapse of the disease and drug resistance are observed. Over the past years, these women have been treated with chemotherapy and cytoreductive surgeries. However, the chemotherapy could affect the healthy tissues in addition to the malignancies. Therefore, discovering new diagnostic and therapeutic options seems to be a crucial need. Unlike the common invasive and/or nonspecific treatments, nanomedicine is trying to find a new way for cancer imaging, diagnosis, and drug delivery method. Nanoparticles (NPs), which has recently drawn attention, can be used in order to reduce the toxicity and frequent dosing of drugs, tumor‐specific delivery, and early diagnosis for malignancies. Chitosan as an NP and product of chitin deacetylation has multiple characteristics, including biocompatibility, biodegradability, and safety. In this review, we cover the studies concerned with the role of chitosan in finding solutions to overcome the problems faced in ovarian cancer treatments. Furthermore, we highlight how chitosan is being used in delivering chemotherapy drugs, gene therapy, and imaging methods for both detection and image‐guided therapies.

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Chitosan promotes cancer progression and stem cell properties in association with Wnt signaling in colon and hepatocellular carcinoma cells

Cited by 45 publications

References 61 publications

KAP1 inhibits the Raf‐MEK‐ERK pathway to promote tumorigenesis in A549 lung cancer cells

KAP1 inhibits the Raf‐MEK‐ERK pathway to promote tumorigenesis in A549 lung cancer cells

Cancer stem cells and fibroblast niche cross talk in an in‐vitro oral dysplasia model

Chitosan is a potential inhibitor of ovarian cancer: Molecular aspects

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