AIM2 inhibits colorectal cancer cell proliferation and migration through suppression of Gli1

Xu, Menglin; Wang, Junfeng; Li, Haoran; Zhang, Zhengrong; Cheng, Zhengwu

doi:10.18632/aging.202226

Cited by 22 publications

(21 citation statements)

References 31 publications

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“…IHC staining of paraffin-embedded human tissues was carried out as reported previously 25 , 26 . In brief, Samples were dewaxed, rehydrated and endogenous peroxidase activity was blocked with 3% hydrogen dioxide.…”

Section: Methodsmentioning

confidence: 99%

“…The Lentivirus vectors carrying LATS1 overexpression or short hairpin RNA (shRNA) targeting LATS1 and their control vectors were invented by Genechem Company (Shanghai, China). We performed the transfection following the company's instructions, which were documented in our earlier study 25 , 26 . Lipofectamine RNAiMax (Invitrogen) was used to transfect small interfering RNA (siRNA) at 20 nM of final concentration, as directed by the manufacturer.…”

Section: Methodsmentioning

confidence: 99%

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LATS1 exerts tumor suppressor functions via targeting Gli1 in colorectal cancer

Shen¹,

Pan²,

Chen³

et al. 2021

J. Cancer

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Background: The Hippo pathway's primary kinase component, large tumor suppressor 1 (LATS1), has been hypothesized as a tumor suppressor in a variety of cancers. LATS1's biological effects on colorectal cancer (CRC) are yet to be determined. Methods: The analysis of LATS1 mRNA expression in CRC was conducted using public databases from the Gene Expressing Profiling Interactive Analysis database (GEPIA). Investigation for the expression of LATS1 protein in 102 CRC tumor tissues and 57 normal tissues was performed using immunohistochemistry (IHC) analysis. In vitro genetic manipulation was used to explore the potential role and mechanism of LATS1 in the regulation of proliferation and migration of CRC cells. Results: LATS1 was found to be considerably downregulated in CRC tissues, with much lower levels in individuals with bigger tumors of size (≥5 cm), deeper invasion (T3-4), positive lymph node metastasis (LNM), and advanced tumor-node-metastasis (TNM) stage (III-IV). As exhibited by clinical data analysis, LATS1 loss was significantly associated with TNM and LNM staging in CRC patients. Furthermore, our in vitro investigations revealed that LATS1 depletion increased CRC cell proliferation and migration in HCT116 cells, whereas overexpressing LATS1 had the opposite effect in SW620 cells. LATS1 suppressed the expression of glioma-associated oncogene-1 (Gli1), and LATS1's tumor-suppressive actions in CRC are dependent on Gli1. Moreover, LATS1 could modulate Yes-associated protein 1 (YAP1) expression and mTOR activation in CRC cells. Conclusion: Our findings identify the LATS1 as a unique Gli1 regulator in CRC cell migration and proliferation, and suggest that LATS1 may serve as a potential therapeutic target for CRC.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

LATS1 exerts tumor suppressor functions via targeting Gli1 in colorectal cancer

Shen¹,

Pan²,

Chen³

et al. 2021

J. Cancer

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“…The glioma-associated oncogene-1 (Gli1) is a tumor-promoting factor that its upregulation enhances growth and invasion of colorectal cancer cells [ 394 ]. Noteworthy, Gli1 participates in enhancing CSCs features and mediating tumor progression [ 395 ].…”

Section: Dietary Agents and Cancer Stem Cellsmentioning

confidence: 99%

Targeting Cancer Stem Cells by Dietary Agents: An Important Therapeutic Strategy against Human Malignancies

Paskeh

Asadi²,

Zabolian

et al. 2021

IJMS

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As a multifactorial disease, treatment of cancer depends on understanding unique mechanisms involved in its progression. The cancer stem cells (CSCs) are responsible for tumor stemness and by enhancing colony formation, proliferation as well as metastasis, and these cells can also mediate resistance to therapy. Furthermore, the presence of CSCs leads to cancer recurrence and therefore their complete eradication can have immense therapeutic benefits. The present review focuses on targeting CSCs by natural products in cancer therapy. The growth and colony formation capacities of CSCs have been reported can be attenuated by the dietary agents. These compounds can induce apoptosis in CSCs and reduce tumor migration and invasion via EMT inhibition. A variety of molecular pathways including STAT3, Wnt/β-catenin, Sonic Hedgehog, Gli1 and NF-κB undergo down-regulation by dietary agents in suppressing CSC features. Upon exposure to natural agents, a significant decrease occurs in levels of CSC markers including CD44, CD133, ALDH1, Oct4 and Nanog to impair cancer stemness. Furthermore, CSC suppression by dietary agents can enhance sensitivity of tumors to chemotherapy and radiotherapy. In addition to in vitro studies, as well as experiments on the different preclinical models have shown capacity of natural products in suppressing cancer stemness. Furthermore, use of nanostructures for improving therapeutic impact of dietary agents is recommended to rapidly translate preclinical findings for clinical use.

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“…For instance, loss of TGFBR2 activity promotes an inflammatory response within the TME by inhibiting anti-inflammatory cytokines, increasing tumor-associated macrophage infiltration and NK T-cell activation (48). AIM2 on the other hand has been indicated to have tumor suppressive properties via promotion of an inflammatory response and inhibition of CRC cell proliferation and migration, similar to myristoylated alanine-rich protein kinase C substrate, another identified FSP that inhibits the proliferation of CRC (49)(50)(51). Inactivating mutation of these genes in MSI-H/dMMR mCRC may thus not result in promoting anti-tumor activity but may at least offer potential targets for precision therapy along with ICIs.…”

Section: Immunotherapy In Crc: Molecular Overview and Rationalementioning

confidence: 99%

Advances in immune therapies for the treatment of microsatellite instability‑high/deficient mismatch repair metastatic colorectal cancer (Review)

et al. 2021

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Microsatellite instability-high/deficient mismatch repair colorectal cancer (MSI-H/dMMR CRC) is a molecular subtype characterized by high-frequency mutations within DNA mismatch repair genes. Defects in the DNA mismatch repair machinery lead to subsequent frame-shift mutations, resulting in the generation of frame-shift peptides that serve as neoantigens. This has translated into exquisite sensitivity to immune checkpoint inhibitors (ICIs) and a significant clinical benefit from immune therapies in this patient population. The present article provides a comprehensive review of the advances in the field of immune therapies for MSI-H/dMMR metastatic CRC, with a focus on the major randomized clinical trials that led to Food and Drug Administration approval of specific ICIs for this population, a detailed review of the molecular background responsible for tumor response, as well as the mechanisms of resistance to ICI therapy. Finally, ongoing investigations of other immunotherapeutic strategies to address and overcome the challenges that currently limit response and long-term response to ICIs were presented.

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AIM2 inhibits colorectal cancer cell proliferation and migration through suppression of Gli1

Cited by 22 publications

References 31 publications

LATS1 exerts tumor suppressor functions via targeting Gli1 in colorectal cancer

LATS1 exerts tumor suppressor functions via targeting Gli1 in colorectal cancer

Targeting Cancer Stem Cells by Dietary Agents: An Important Therapeutic Strategy against Human Malignancies

Advances in immune therapies for the treatment of microsatellite instability‑high/deficient mismatch repair metastatic colorectal cancer (Review)

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