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Article ; Online: Inhibition of LATS kinases reduces tumorigenicity and increases the sensitivity of human chronic myelogenous leukemia cells to imatinib.

Klaihmon, Phatchanat / Lorthongpanich, Chanchao / Kheolamai, Pakpoom / Saisaard, Wannachai / Issaragrisil, Surapol

2024 Volume 14, Issue 1, Page(s) 3993

Abstract: Chronic myelogenous leukemia (CML) is a clonal hematologic malignancy of the myeloid lineage caused by the oncogenic BCR/ABL fusion protein that promotes CML cell proliferation and protects them against drug-induced apoptosis. In this study, we determine ...

Abstract	Chronic myelogenous leukemia (CML) is a clonal hematologic malignancy of the myeloid lineage caused by the oncogenic BCR/ABL fusion protein that promotes CML cell proliferation and protects them against drug-induced apoptosis. In this study, we determine LATS1 and LATS2 expression in CML cells derived from patients who are resistant to imatinib (IM) treatment. Significant upregulation of LATS1 and LATS2 was found in these CML patients compared to healthy donors. To further explore whether the expression of LATS1/2 contributes to the IM-resistant phenotype, IM-resistant CML cell lines generated by culturing CML-derived erythroblastic K562 cells in increasing concentrations of IM were used as in vitro models. Up-regulation of LATS1 and LATS2 was observed in IM-resistant K562 cells. Reduction of LATS using either Lats-IN-1 (TRULI), a specific LATS inhibitor, or shRNA targeting LATS1/2 significantly reduced clonogenicity, increased apoptosis and induced differentiation of K562 cells to late-stage erythroid cells. Furthermore, depletion of LATS1 and LATS2 also increased the sensitivity of K562 cells to IM. Taken together, our results suggest that LATS could be one of the key factors contributing to the rapid proliferation, reduced apoptosis, and IM resistance of CML cells. Targeting LATS could be a promising treatment to enhance the therapeutic effect of a conventional BCR/ABL tyrosine kinase inhibitor such as IM.
MeSH term(s)	Humans ; Imatinib Mesylate/pharmacology ; Imatinib Mesylate/therapeutic use ; Drug Resistance, Neoplasm ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/pathology ; Fusion Proteins, bcr-abl/genetics ; Protein Serine-Threonine Kinases ; K562 Cells ; Apoptosis ; Tumor Suppressor Proteins
Chemical Substances	Imatinib Mesylate (8A1O1M485B) ; Fusion Proteins, bcr-abl (EC 2.7.10.2) ; Protein Serine-Threonine Kinases (EC 2.7.11.1) ; LATS2 protein, human (EC 2.7.1.11) ; Tumor Suppressor Proteins
Language	English
Publishing date	2024-02-18
Publishing country	England
Document type	Journal Article
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-024-54728-z
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Article ; Online: Role of YAP as a Mechanosensing Molecule in Stem Cells and Stem Cell-Derived Hematopoietic Cells.

Damkham, Nattaya / Issaragrisil, Surapol / Lorthongpanich, Chanchao

International journal of molecular sciences

2022 Volume 23, Issue 23

Abstract: Yes-associated protein (YAP) and WW domain-containing transcription regulator protein 1 (WWTR1, also known as TAZ) are transcriptional coactivators in the Hippo signaling pathway. Both are well-known regulators of cell proliferation and organ size ... ...

Abstract	Yes-associated protein (YAP) and WW domain-containing transcription regulator protein 1 (WWTR1, also known as TAZ) are transcriptional coactivators in the Hippo signaling pathway. Both are well-known regulators of cell proliferation and organ size control, and they have significant roles in promoting cell proliferation and differentiation. The roles of YAP and TAZ in stem cell pluripotency and differentiation have been extensively studied. However, the upstream mediators of YAP and TAZ are not well understood. Recently, a novel role of YAP in mechanosensing and mechanotransduction has been reported. The present review updates information on the regulation of YAP by mechanical cues such as extracellular matrix stiffness, fluid shear stress, and actin cytoskeleton tension in stem cell behaviors and differentiation. The review explores mesenchymal stem cell fate decisions, pluripotent stem cells (PSCs), self-renewal, pluripotency, and differentiation to blood products. Understanding how cells sense their microenvironment or niche and mimic those microenvironments in vitro could improve the efficiency of producing stem cell products and the efficacy of the products.
Language	English
Publishing date	2022-11-23
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms232314634
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Article ; Online: Role of YAP as a Mechanosensing Molecule in Stem Cells and Stem Cell-Derived Hematopoietic Cells

Nattaya Damkham / Surapol Issaragrisil / Chanchao Lorthongpanich

International Journal of Molecular Sciences, Vol 23, Iss 14634, p

2022 Volume 14634

Abstract	Yes-associated protein (YAP) and WW domain-containing transcription regulator protein 1 (WWTR1, also known as TAZ) are transcriptional coactivators in the Hippo signaling pathway. Both are well-known regulators of cell proliferation and organ size control, and they have significant roles in promoting cell proliferation and differentiation. The roles of YAP and TAZ in stem cell pluripotency and differentiation have been extensively studied. However, the upstream mediators of YAP and TAZ are not well understood. Recently, a novel role of YAP in mechanosensing and mechanotransduction has been reported. The present review updates information on the regulation of YAP by mechanical cues such as extracellular matrix stiffness, fluid shear stress, and actin cytoskeleton tension in stem cell behaviors and differentiation. The review explores mesenchymal stem cell fate decisions, pluripotent stem cells (PSCs), self-renewal, pluripotency, and differentiation to blood products. Understanding how cells sense their microenvironment or niche and mimic those microenvironments in vitro could improve the efficiency of producing stem cell products and the efficacy of the products.
Keywords	YAP ; stem cells ; differentiation ; hematopoietic stem cells ; mechanical forces ; mechanosensing ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	571
Language	English
Publishing date	2022-11-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
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Article: Distinctive Roles of YAP and TAZ in Human Endothelial Progenitor Cells Growth and Functions.

Klaihmon, Phatchanat / Lorthongpanich, Chanchao / Kheolamai, Pakpoom / Luanpitpong, Sudjit / Issaragrisil, Surapol

Biomedicines

2022 Volume 10, Issue 1

Abstract: The hippo signaling pathway plays an essential role in controlling organ size and balancing tissue homeostasis. Its two main effectors, yes-associated protein (YAP) and WW domain-containing transcription regulator 1, WWTR1 or TAZ, have also been shown to ...

Abstract	The hippo signaling pathway plays an essential role in controlling organ size and balancing tissue homeostasis. Its two main effectors, yes-associated protein (YAP) and WW domain-containing transcription regulator 1, WWTR1 or TAZ, have also been shown to regulate endothelial cell functions and angiogenesis. In this study, the functions of YAP and TAZ in human endothelial progenitor cells (EPCs) were investigated by a loss-of-function study using CRISPR/Cas9-mediated gene knockdown (KD). Depletion of either YAP or TAZ reduced EPC survival and impaired many of their critical functions, including migration, invasion, vessel-formation, and expression of pro-angiogenic genes. Notably, TAZ-KD EPCs exhibited more severe phenotypes in comparison to YAP-KD EPCs. Moreover, the conditioned medium derived from TAZ-KD EPCs reduced the survivability of human lung cancer cells and increased their sensitivity to chemotherapeutic agents. The overexpression of either wild-type or constitutively active TAZ rescued the impaired phenotypes of TAZ-KD EPCs and restored the expression of pro-angiogenic genes in those EPCs. In summary, we demonstrate the crucial role of Hippo signaling components, YAP and TAZ, in controlling several aspects of EPC functions that can potentially be used as a drug target to enhance EPC functions in patients.
Language	English
Publishing date	2022-01-11
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2720867-9
ISSN	2227-9059
ISSN	2227-9059
DOI	10.3390/biomedicines10010147
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Article ; Online: Synthesis of Cationic Quaternized Nanolevan Derivative for Small Molecule and Nucleic Acid Delivery.

Charoenwongphaibun, Chonnipha / Lorthongpanich, Chanchao / Septham, Prapasri / Wangpaiboon, Karan / Panpetch, Pawinee / Pichyangkura, Rath / Charoenwongpaiboon, Thanapon / Kuttiyawong, Kamontip

Gels (Basel, Switzerland)

2023 Volume 9, Issue 3

Abstract: Levan is a biopolymer composed of fructose chains covalently linked by β-2,6 glycosidic linkages. This polymer self-assembles into a nanoparticle of uniform size, making it useful for a wide range of applications. Also, levan exhibits various biological ... ...

Abstract	Levan is a biopolymer composed of fructose chains covalently linked by β-2,6 glycosidic linkages. This polymer self-assembles into a nanoparticle of uniform size, making it useful for a wide range of applications. Also, levan exhibits various biological activities such as antioxidants, anti-inflammatory, and anti-tumor, that make this polymer very attractive for biomedical application. In this study, levan synthesized from
Language	English
Publishing date	2023-02-28
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2813982-3
ISSN	2310-2861 ; 2310-2861
ISSN (online)	2310-2861
ISSN	2310-2861
DOI	10.3390/gels9030188
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Article ; Online: Distinctive Roles of YAP and TAZ in Human Endothelial Progenitor Cells Growth and Functions

Phatchanat Klaihmon / Chanchao Lorthongpanich / Pakpoom Kheolamai / Sudjit Luanpitpong / Surapol Issaragrisil

Biomedicines, Vol 10, Iss 147, p

2022 Volume 147

Abstract	The hippo signaling pathway plays an essential role in controlling organ size and balancing tissue homeostasis. Its two main effectors, yes-associated protein (YAP) and WW domain-containing transcription regulator 1, WWTR1 or TAZ, have also been shown to regulate endothelial cell functions and angiogenesis. In this study, the functions of YAP and TAZ in human endothelial progenitor cells (EPCs) were investigated by a loss-of-function study using CRISPR/Cas9-mediated gene knockdown (KD). Depletion of either YAP or TAZ reduced EPC survival and impaired many of their critical functions, including migration, invasion, vessel-formation, and expression of pro-angiogenic genes. Notably, TAZ-KD EPCs exhibited more severe phenotypes in comparison to YAP-KD EPCs. Moreover, the conditioned medium derived from TAZ-KD EPCs reduced the survivability of human lung cancer cells and increased their sensitivity to chemotherapeutic agents. The overexpression of either wild-type or constitutively active TAZ rescued the impaired phenotypes of TAZ-KD EPCs and restored the expression of pro-angiogenic genes in those EPCs. In summary, we demonstrate the crucial role of Hippo signaling components, YAP and TAZ, in controlling several aspects of EPC functions that can potentially be used as a drug target to enhance EPC functions in patients.
Keywords	hippo signaling pathway ; endothelial progenitor cells ; YAP/TAZ ; Biology (General) ; QH301-705.5
Subject code	572
Language	English
Publishing date	2022-01-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
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Article ; Online: Generation of RUNX1c-eGFP induced pluripotent stem cell, MUSIi012-A-4, using CRISPR/Cas9.

Srisook, Pimonwan / Laowtammathron, Chuti / Lorthongpanich, Chanchao / Klaihmon, Phatchanat / Terbto, Papussorn / Waeteekul, Supaporn / U-Pratya, Yaowalak / Issaragrisil, Surapol

Stem cell research

2023 Volume 67, Page(s) 103035

Abstract: Runt-Related Transcription Factor 1c (RUNX1c) plays an important role in regulating the development of hematopoietic stem cells (HSC). Using CRISPR/Cas9 gene editing technology, we established a RUNX1c-eGFP reporter cell line from the MUSIi012-A cell ... ...

Abstract	Runt-Related Transcription Factor 1c (RUNX1c) plays an important role in regulating the development of hematopoietic stem cells (HSC). Using CRISPR/Cas9 gene editing technology, we established a RUNX1c-eGFP reporter cell line from the MUSIi012-A cell line. The MUSIi012-A-4 cell line has normal stem cell morphology and karyotype, expresses pluripotency markers, and can be differentiated into all three germ layers in vitro and in vivo. This cell line serves as a valuable model to observe the expression of RUNX1c via eGFP tracking during human hematopoietic development.
MeSH term(s)	Humans ; Induced Pluripotent Stem Cells/metabolism ; CRISPR-Cas Systems ; Cell Line ; Gene Editing ; Cell Differentiation
Language	English
Publishing date	2023-01-25
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2393143-7
ISSN	1876-7753 ; 1873-5061
ISSN (online)	1876-7753
ISSN	1873-5061
DOI	10.1016/j.scr.2023.103035
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Article ; Online: Production and bioactivities of nanoparticulated and ultrasonic-degraded levan generated by Erwinia tasmaniensis levansucrase in human osteosarcoma cells.

Charoenwongpaiboon, Thanapon / Wangpaiboon, Karan / Septham, Prapasri / Jiamvoraphong, Nittaya / Issaragrisil, Surapol / Pichyangkura, Rath / Lorthongpanich, Chanchao

International journal of biological macromolecules

2022 Volume 221, Page(s) 1121–1129

Abstract: Levan is a bioactive polysaccharide that can be synthesized by various microorganisms. In this study, the physicochemical properties and bioactivity of levan synthesized by recombinant levansucrase from Erwinia tasmaniensis were investigated. The ... ...

Abstract	Levan is a bioactive polysaccharide that can be synthesized by various microorganisms. In this study, the physicochemical properties and bioactivity of levan synthesized by recombinant levansucrase from Erwinia tasmaniensis were investigated. The synthesis conditions, including the enzyme concentration, substrate concentration, and temperature, were optimized. The obtained levan generally appeared as a cloudy suspension. However, it could transform into a hydrogel at concentrations exceeding 10 % (w/v). Then, ultrasonication was utilized to reduce the molecular weight and increase the bioavailability of levan. Dynamic light scattering (DLS) and gel permeation chromatography (GPC) indicated that the size of levan was significantly decreased by ultrasonication, whereas Fourier transform infrared spectroscopy,
MeSH term(s)	Humans ; Ultrasonics ; Hexosyltransferases/chemistry ; Fructans/chemistry ; Osteosarcoma
Chemical Substances	levansucrase (EC 2.4.1.10) ; Hexosyltransferases (EC 2.4.1.-) ; Fructans
Language	English
Publishing date	2022-09-15
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	282732-3
ISSN	1879-0003 ; 0141-8130
ISSN (online)	1879-0003
ISSN	0141-8130
DOI	10.1016/j.ijbiomac.2022.09.096
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Article: Intermittent compressive force regulates human periodontal ligament cell behavior via yes-associated protein.

Klincumhom, Nuttha / Lorthongpanich, Chanchao / Thumanu, Kanjana / Septham, Praphasri / Phomyu, Wutthikiat / Issaragrisil, Surapol / Pavasant, Prasit

Heliyon

2022 Volume 8, Issue 10, Page(s) e10845

Abstract: Intermittent compressive force influences human periodontal ligament (PDL) cell behavior that facilitates periodontal tissue regeneration. In response to mechanical stimuli, Yes-associated protein (YAP) has been recognized as a mechanosensitive ... ...

Abstract	Intermittent compressive force influences human periodontal ligament (PDL) cell behavior that facilitates periodontal tissue regeneration. In response to mechanical stimuli, Yes-associated protein (YAP) has been recognized as a mechanosensitive transcriptional activator that regulates cell proliferation and cell fate decisions. This study aimed to investigate whether compressive forces influence cell proliferation and cell fate decisions of human PDL cells via YAP signaling. YAP expression was silenced by shRNA. The effect of YAP on cell proliferation, adipogenesis and osteogenesis of PDL cells under ICF loading were determined. Adipogenic differentiation bias upon ICF loading was confirmed by fourier-transform infrared spectroscopy (FTIR). The results revealed that ICF-induced YAP promotes osteogenesis, but it inhibits adipogenesis in PDL cells. Depletion of YAP results in PDL cells that are irresponsive to ICF and, therefore, the failure of the PDL cells to undergo osteogenic differentiation. This was shown by a significant reduction in calcium deposited in the CF-derived osteoblasts of the YAP-knockdown (YAP-KD) PDL cells. As to control treatment, reduction of YAP promoted adipogenesis, whereas ICF-induced YAP inhibited this mechanism. However, the adipocyte differentiation in YAP-KD cells was not affected upon ICF treatment as the YAP-KD cells still exhibited a better adipogenic differentiation that was unrelated to the ICF. This study demonstrated that, in response to ICF treatment, YAP could be a crucial mechanosensitive transcriptional activator for the regulation of PDL cell behavior through a mechanobiological process. Our results may provide the possibility of facilitating PDL tissue regeneration by manipulation of the Hippo-YAP signaling pathway.
Language	English
Publishing date	2022-10-01
Publishing country	England
Document type	Journal Article
ZDB-ID	2835763-2
ISSN	2405-8440
ISSN	2405-8440
DOI	10.1016/j.heliyon.2022.e10845
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Article ; Online: Role of YAP in hematopoietic differentiation and erythroid lineage specification of human-induced pluripotent stem cells.

Laowtammathron, Chuti / Lorthongpanich, Chanchao / Jiamvoraphong, Nittaya / Srisook, Pimonwan / Klaihmon, Phatchanat / Kheolamai, Pakpoom / Luanpitpong, Sudjit / Issaragrisil, Surapol

Stem cell research & therapy

2023 Volume 14, Issue 1, Page(s) 279

Abstract: Background: In vitro production of hematopoietic stem/progenitor cells (HSPCs) from human-induced pluripotent stem cells (hiPSCs) provides opportunities for fundamental research, disease modeling, and large-scale production of HLA-matched HSPCs for ... ...

Abstract	Background: In vitro production of hematopoietic stem/progenitor cells (HSPCs) from human-induced pluripotent stem cells (hiPSCs) provides opportunities for fundamental research, disease modeling, and large-scale production of HLA-matched HSPCs for therapeutic applications. However, a comprehensive understanding of the signaling mechanisms that regulate human hematopoiesis is needed to develop a more effective procedure for deriving HSPCs from hiPSCs. Methods: In this study, we investigate the role of YAP during the hematopoietic differentiation of hiPSCs to HSPCs and erythrocytes using the isogenic YAP-overexpressing (YAP-S5A) and YAP-depleting (YAP-KD) hiPSCs to eliminate the effects of a genetic background variation. Results: Although YAP is dispensable for maintaining the self-renewal and pluripotency of these hiPSCs, it affects the early cell-fate determination and hematopoietic differentiation of hiPSCs. Depleting YAP enhances the derivation efficiency of HSPCs from hiPSCs by inducing the mesodermal lineage commitment, promoting hematopoietic differentiation, and preventing the differentiation toward endothelial lineage. On the contrary, the overexpression of YAP reduced HSPCs yield by inducing the endodermal lineage commitment, suppressing hematopoietic differentiation, and promoting the differentiation toward endothelial lineage. Conclusions: Expression of YAP is crucial for the differentiation of hiPSC-derived HSPCs toward mature erythrocytes. We believe that by manipulating YAP activity using small molecules, the efficiency of the large-scale in vitro production system for generating hematopoietic stem/progenitor cells for future therapeutic use could be improved.
MeSH term(s)	Humans ; Induced Pluripotent Stem Cells/metabolism ; Cell Lineage/genetics ; Cell Differentiation/genetics ; Hematopoietic Stem Cells/metabolism ; Hematopoiesis
Language	English
Publishing date	2023-09-29
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2548671-8
ISSN	1757-6512 ; 1757-6512
ISSN (online)	1757-6512
ISSN	1757-6512
DOI	10.1186/s13287-023-03508-z
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