E‐cadherin‐Fc chimera protein matrix enhances cancer stem‐like properties and induces mesenchymal features in colon cancer cells

Qian, Yamin; Wu, Xin; Yokoyama, Yuhki; Okuzaki, Daisuke; Taguchi, M.; Hirose, Haruka; Wang, Jiaqi; Hata, Tsuyoshi; Hiraki, Masayuki; Ohtsuka, Masahisa; Takahashi, Hidekazu; Haraguchi, Naotsugu; Mizushima, Tsunekazu; Tanaka, Shinji; Mori, Masaki; Yamamoto, Hirofumi

doi:10.1111/cas.14193

Cited by 14 publications

(14 citation statements)

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“…E-cadherin is a calcium-dependent transmembrane cell adhesion molecule, which plays a key role in maintaining epithelial polarity and integrity. Previous studies proved that loss of E-cadherin could promote the invasion and metastasis of tumor, which was also related to poor prognosis in patients with breast, colon, and other cancers [ 26 , 27 ]. The results from the current study showed that ANKRD22 contributed to breast cancer progression, indicating that it might act as a potential marker for the therapy of breast cancer.…”

Section: Discussionmentioning

confidence: 99%

ANKRD22 enhances breast cancer cell malignancy by activating the Wnt/β-catenin pathway via modulating NuSAP1 expression

Liu

Gong

et al. 2020

Bosn J of Basic Med Sci

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Breast cancer is one of the most prevalent malignancies in women worldwide. Although great progress has been achieved in the diagnosis and treatment of breast cancer, the prognosis of patients with breast cancer is still poor due to distal recurrence and metastasis after surgery. This study demonstrated that the expression level of ankyrin repeat domain 22 (ANKRD22) in human breast cancer tissues was significantly higher than that in normal breast tissues. ANKRD22 knockdown inhibited the proliferation, invasion, and epithelial-mesenchymal transition (EMT) of breast cancer cells. Further research indicated that ANKRD22 regulated the expression of nucleolar and spindle-associated protein 1 (NuSAP1) and then the activation of Wnt/β-catenin signaling pathway. Moreover, overexpression of NuSAP1 reversed the inhibitory effects of ANKRD22 knockdown on the proliferation, invasion, and EMT of breast cancer cells. In summary, this study demonstrated that ANKRD22 enhanced breast cancer cell malignancy by activating the Wnt/β-catenin pathway via modulating NuSAP1 expression, which might shed light on new therapeutic approaches for breast cancer.

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Section: Discussionmentioning

confidence: 99%

ANKRD22 enhances breast cancer cell malignancy by activating the Wnt/β-catenin pathway via modulating NuSAP1 expression

Liu

Gong

et al. 2020

Bosn J of Basic Med Sci

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“…Activation of the EGFR pathway also contributes to the chemoresistance of CRC by inducing EMT and enriching the CSC population [ 249 ]. Similarly, the reduced expression of this pathway’s inhibitors, such as VPS33B, has been associated with poorer prognosis in patients and increased resistance to oxaliplatin in vitro and in vivo [ 236 ].…”

Section: Phenotype Transition (Moc-7)mentioning

confidence: 99%

Cellular Mechanisms Accounting for the Refractoriness of Colorectal Carcinoma to Pharmacological Treatment

Marin

Macı́as

Monte

et al. 2020

Cancers

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The unsatisfactory response of colorectal cancer (CRC) to pharmacological treatment contributes to the substantial global health burden caused by this disease. Over the last few decades, CRC has become the cause of more than 800,000 deaths per year. The reason is a combination of two factors: (i) the late cancer detection, which is being partially solved by the implementation of mass screening of adults over age 50, permitting earlier diagnosis and treatment; (ii) the inadequate response of advanced unresectable tumors (i.e., stages III and IV) to pharmacological therapy. The latter is due to the existence of complex mechanisms of chemoresistance (MOCs) that interact and synergize with each other, rendering CRC cells strongly refractory to the available pharmacological regimens based on conventional chemotherapy, such as pyrimidine analogs (5-fluorouracil, capecitabine, trifluridine, and tipiracil), oxaliplatin, and irinotecan, as well as drugs targeted toward tyrosine kinase receptors (regorafenib, aflibercept, bevacizumab, cetuximab, panitumumab, and ramucirumab), and, more recently, immune checkpoint inhibitors (nivolumab, ipilimumab, and pembrolizumab). In the present review, we have inventoried the genes involved in the lack of CRC response to pharmacological treatment, classifying them into seven groups (from MOC-1 to MOC-7) according to functional criteria to identify cancer cell weaknesses. This classification will be useful to pave the way for developing sensitizing tools consisting of (i) new agents to be co-administered with the active drug; (ii) pharmacological approaches, such as drug encapsulation (e.g., into labeled liposomes or exosomes); (iii) gene therapy interventions aimed at restoring the impaired function of some proteins (e.g., uptake transporters and tumor suppressors) or abolishing that of others (such as export pumps and oncogenes).

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“…The oncogenic role of SOX9 is related to several cell signaling pathways, such as the TGFβ/Smad, Notch and Wnt/β-catenin pathways (Li and Neaves, 2006;Abdul Khalek et al, 2010). Studies have confirmed that SOX9-overexpressing cancer cells are resistant to oxaliplatin (Anuja et al, 2019;Qian et al, 2019;Abad et al, 2020;Das et al, 2020). However, the underlying mechanism of SOX9 in resistance to oxaliplatin is still unclear.…”

Section: Introductionmentioning

confidence: 99%

The SOX9-MMS22L Axis Promotes Oxaliplatin Resistance in Colorectal Cancer

Liu

Luo

et al. 2021

Front. Mol. Biosci.

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BackgroundColorectal cancer (CRC) is estimated to be one of the most common cancers and the leading cause of cancer-related death worldwide. SOX9 is commonly overexpressed in CRC and participates in drug resistance. In addition, DNA damage repair confers resistance to anticancer drugs. However, the correlation between DNA damage repair and high SOX9 expression is still unclear. In this study, we aimed to investigate the function and the specific underlying mechanism of the SOX9-dependent DNA damage repair pathway in CRC.MethodsThe expression levels of SOX9 and MMS22L in CRC were examined by immunohistochemistry (IHC) and TCGA analysis. RNA sequencing was conducted in RKO SOX9-deficient cells and RKO shControl cells. Mechanistic studies were performed in CRC cells by modulating SOX9 and MMS22L expression, and we evaluated drug sensitivity and DNA damage repair signaling events. In addition, we investigated the effect of oxaliplatin in tumors with SOX9 overexpression and low expression of MMS22L in vivo.ResultsOur study showed that SOX9 has a higher expression level in CRC tissues than in normal tissues and predicts poor prognosis in CRC patients. Overexpression and knockdown of SOX9 were associated with the efficacy of oxaliplatin. In addition, SOX9 activity was enriched in the DNA damage repair pathway via regulation of MMS22L expression and participation in DNA double-strand break repair. SOX9 was upregulated and formed a complex with MMS22L, which promoted the nuclear translocation of MMS22L upon oxaliplatin treatment. Moreover, the xenograft assay results showed that oxaliplatin abrogated tumor growth from cells with MMS22L downregulation in mice.ConclusionsIn CRC, activation of the SOX9-MMS22L-dependent DNA damage pathway is a core pathway regulating oxaliplatin sensitivity. Targeting this pathway in oxaliplatin-resistant CRC cells is a promising therapeutic option.

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E‐cadherin‐Fc chimera protein matrix enhances cancer stem‐like properties and induces mesenchymal features in colon cancer cells

Cited by 14 publications

References 64 publications

ANKRD22 enhances breast cancer cell malignancy by activating the Wnt/β-catenin pathway via modulating NuSAP1 expression

ANKRD22 enhances breast cancer cell malignancy by activating the Wnt/β-catenin pathway via modulating NuSAP1 expression

Cellular Mechanisms Accounting for the Refractoriness of Colorectal Carcinoma to Pharmacological Treatment

The SOX9-MMS22L Axis Promotes Oxaliplatin Resistance in Colorectal Cancer

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