PTEN, a Barrier for Proliferation and Metastasis of Gastric Cancer Cells: From Molecular Pathways to Targeting and Regulation

Ashrafizadeh, Milad; Najafi, Masoud; Ang, Hui Li; Moghadam, Ebrahim Rahmani; Mahabady, Mahmood Khaksary; Zabolian, Amirhossein; Jafaripour, Leila; Bejandi, Atefe Kazemzade; Hushmandi, Kiavash; Saleki, Hossein; Zarrabi, Ali; Kumar, Alan Prem

doi:10.3390/biomedicines8080264

Cited by 47 publications

(31 citation statements)

References 263 publications

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“…This plays a pivotal role in cell movement, division, membrane organization, and cancer progression, all of which require the coordinated turnover and remodeling of the actin filaments [ 18 ]. The polymerization is associated with the formation of flat, sheet-like membrane protrusions called lamellipodia, or finger-like extensions at the edge of lamellipodia called filopodia [ 19 ]. In lamellipodia, actin filaments are arranged in a loosely organized meshwork, often referred to as dendritic networks [ 20 ], whereas, in filopodia, actin filaments arrange into parallel bundles [ 21 ].…”

Section: Role Of Cellular Cytoskeleton In Emtmentioning

confidence: 99%

“…In order to do so, the epithelial cancer cells need first to lose their cell-cell junctions and become motile. This is followed by the degradation of the underlying basement membrane and ECM [ 18 , 19 , 20 ]. The ability to degrade the ECM and invade into the surrounding tissue parenchyma is obtained by activating the EMT program, where the epithelial cancer cells transform into a more invasive and motile mesenchymal state [ 21 , 22 ].…”

Section: Introductionmentioning

confidence: 99%

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Cytoskeletal Dynamics in Epithelial-Mesenchymal Transition: Insights into Therapeutic Targets for Cancer Metastasis

Datta

Deng

Gopal

et al. 2021

Cancers

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In cancer cells, a vital cellular process during metastasis is the transformation of epithelial cells towards motile mesenchymal cells called the epithelial to mesenchymal transition (EMT). The cytoskeleton is an active network of three intracellular filaments: actin cytoskeleton, microtubules, and intermediate filaments. These filaments play a central role in the structural design and cell behavior and are necessary for EMT. During EMT, epithelial cells undergo a cellular transformation as manifested by cell elongation, migration, and invasion, coordinated by actin cytoskeleton reorganization. The actin cytoskeleton is an extremely dynamic structure, controlled by a balance of assembly and disassembly of actin filaments. Actin-binding proteins regulate the process of actin polymerization and depolymerization. Microtubule reorganization also plays an important role in cell migration and polarization. Intermediate filaments are rearranged, switching to a vimentin-rich network, and this protein is used as a marker for a mesenchymal cell. Hence, targeting EMT by regulating the activities of their key components may be a potential solution to metastasis. This review summarizes the research done on the physiological functions of the cytoskeleton, its role in the EMT process, and its effect on multidrug-resistant (MDR) cancer cells—highlight some future perspectives in cancer therapy by targeting cytoskeleton.

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Section: Role Of Cellular Cytoskeleton In Emtmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Cytoskeletal Dynamics in Epithelial-Mesenchymal Transition: Insights into Therapeutic Targets for Cancer Metastasis

Datta

Deng

Gopal

et al. 2021

Cancers

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“…Phosphatidylinositol 3-kinase (PI3K) plays many important biological functions in cell proliferation, cell growth, differentiation and apoptosis. Many studies have illustrated that the PI3K signaling pathway could be abnormally activated in multiple types of cancer [ 20 – 22 ]. Various growth factors and signal transduction complexes activate and phosphorylate the receptor tyrosinase to recruit the p85 subunit of PI3K, phosphorylation of phosphatidylinositol is catalyzed and transformed phosphatidyl inositol triphosphate (PIP3).…”

Section: Introductionmentioning

confidence: 99%

Suppressive effects of plumbagin on the growth of human bladder cancer cells via PI3K/AKT/mTOR signaling pathways and EMT

et al. 2020

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Background Novel chemotherapeutic drugs with good anti-tumor activity are of pressing need for bladder cancer treatment. In this study, plumbagin (PL), a natural plant-derived drug extracted from Chinese herbals, was identified as a promising candidate for human bladder cancer (BCa) chemotherapy. Methods The anti-tumor activity of PL was evaluated using a series of in vitro experiments, such as MTT, transwell assay, flow cytometry, quantitative real-time PCR (qRT-PCR) and western blotting. We established xenograft tumors in nude mice by subcutaneous injection with the human bladder cancer T24 cells. Results The results showed that PL could inhibit the proliferation, migration and survival of BCa cells (T24 and UMUC3 cells) in a time- and dose-dependent way. We found PL promotes the cell cycle arrest and apoptosis by inhibiting PI3K/AKT/mTOR signaling pathway, which inhibits cell proliferation. In vivo, anti-tumor activity of PL was further investigated using a BCa cell xenograft mice model. To simulate clinical chemotherapy, the PL were intravenously injected with a dose of 10 mg/kg for 10 times. Compared with the blank control, the tumor weight in PL treated group decreased significantly from 0.57 ± 0.04 g to 0.21 ± 0.06 g (P < 0.001). Conclusions In our study. We found PL inhibits the proliferation of T24 and UMUC3 cells in vivo and in vitro, which may play a role through several downstream effectors of PI3K/AKT/mTOR signaling pathway to promote the cell cycle arrest and apoptosis. Meanwhile, we consider that PL may inhibit the migration of bladder cancer cells via EMT suppression and induce ROS generation to make cell apoptosis. This work screened out a novel chemotherapeutic drug (plumbagin) with relatively good anti-tumor activity, which possessed great potential in BCa chemotherapy.

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“…PTEN is a tumor suppressor factor with nucleus and cytoplasmic localization with various expressions in healthy and cancerous cells [ 66 , 67 ]. In order to provide a better understanding of PTEN signaling, first, the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) axis should be described.…”

Section: Pten In Oncologymentioning

confidence: 99%

Small in Size, but Large in Action: microRNAs as Potential Modulators of PTEN in Breast and Lung Cancers

et al. 2021

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MicroRNAs (miRNAs) are well-known regulators of biological mechanisms with a small size of 19–24 nucleotides and a single-stranded structure. miRNA dysregulation occurs in cancer progression. miRNAs can function as tumor-suppressing or tumor-promoting factors in cancer via regulating molecular pathways. Breast and lung cancers are two malignant thoracic tumors in which the abnormal expression of miRNAs plays a significant role in their development. Phosphatase and tensin homolog (PTEN) is a tumor-suppressor factor that is capable of suppressing the growth, viability, and metastasis of cancer cells via downregulating phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling. PTEN downregulation occurs in lung and breast cancers to promote PI3K/Akt expression, leading to uncontrolled proliferation, metastasis, and their resistance to chemotherapy and radiotherapy. miRNAs as upstream mediators of PTEN can dually induce/inhibit PTEN signaling in affecting the malignant behavior of lung and breast cancer cells. Furthermore, long non-coding RNAs and circular RNAs can regulate the miRNA/PTEN axis in lung and breast cancer cells. It seems that anti-tumor compounds such as baicalein, propofol, and curcumin can induce PTEN upregulation by affecting miRNAs in suppressing breast and lung cancer progression. These topics are discussed in the current review with a focus on molecular pathways.

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PTEN, a Barrier for Proliferation and Metastasis of Gastric Cancer Cells: From Molecular Pathways to Targeting and Regulation

Cited by 47 publications

References 263 publications

Cytoskeletal Dynamics in Epithelial-Mesenchymal Transition: Insights into Therapeutic Targets for Cancer Metastasis

Cytoskeletal Dynamics in Epithelial-Mesenchymal Transition: Insights into Therapeutic Targets for Cancer Metastasis

Suppressive effects of plumbagin on the growth of human bladder cancer cells via PI3K/AKT/mTOR signaling pathways and EMT

Small in Size, but Large in Action: microRNAs as Potential Modulators of PTEN in Breast and Lung Cancers

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