Src Induces Podoplanin Expression to Promote Cell Migration

Shen, Yongquan; Chen, Chen Shan; Ichikawa, Hitoshi; Goldberg, Gary S.

doi:10.1074/jbc.m109.047696

Cited by 52 publications

(113 citation statements)

References 36 publications

(65 reference statements)

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“…Transfectants were selected with Zeocin (InvivoGen ant-zn-1p) and puromycin (Calbiochem 540411). This double transfection/ selection technique produces high levels of transgene expression in about 80% or more of surviving cells (4,15,19).…”

Section: Methodsmentioning

confidence: 99%

“…Pdpn mutant constructs were produced with the QuikChange II XL site-directed mutagenesis kit according to the manufacturer's protocol (Stratagene 200521). The vector pEF4Pdpn encoding full-length wild type mouse PDPN (PdpnWT) (4,18) was used as a template. Pdpn(S167A/S171A) encoding nonphosphorylatable PDPN (PdpnAA) was generated with the complementary primer pairs 5Ј-GTTGTTATGAAGAAGAT-TGCTGGAAGGTTCTCGCC-3Ј, 5Ј-GGCGAGAACCTTC-CAGCAATCTTCTTCATAACAAC-3Ј followed by 5Ј-TGG-AAGGTTCGCGCCCTAAAGAGGGCCCTTCGAAGG-3Ј, 5Ј-CCTTCGAAGGGCCCTCTTTAGGGCGCGAACCTT-CCA-3Ј.…”

Section: Methodsmentioning

confidence: 99%

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Serines in the Intracellular Tail of Podoplanin (PDPN) Regulate Cell Motility

Krishnan¹,

Ochoa-Alvarez²,

Shen³

et al. 2013

Journal of Biological Chemistry

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Background: PDPN is a transmembrane receptor that promotes cell migration, but modifications that regulate its effects are not known. Results: PKA can phosphorylate PDPN, nonphosphorylatable PDPN promotes cell migration, and phosphomimetic PDPN fails to promote cell migration. Conclusion: PKA can phosphorylate PDPN to decrease cell migration. Significance: PDPN effects on cell motility are important for processes including embryonic development and cancer progression.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Serines in the Intracellular Tail of Podoplanin (PDPN) Regulate Cell Motility

Krishnan¹,

Ochoa-Alvarez²,

Shen³

et al. 2013

Journal of Biological Chemistry

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“…Although recently discovered, experiments indicate that Src induces Tmem163 expression in order to promote cell migration. 127 Increased Tmem163 mRNA expression has also been found in papillary thyroid carcinoma 145 and nodular lymphocytepredominant Hodgkin lymphoma. 146 Vegfr2/Kdr (vascular endothelial growth factor receptor 2/kinase-insert domain receptor) is a receptor tyrosine kinase that plays an important role in tumor growth, invasion, and angiogenesis.…”

Section: Src and Downstream Chemotherapeutic Targetsmentioning

confidence: 99%

“…Indeed, although Src does not require Cas to phosphorylate Cx43, Src does require Cas to block gap junctional communication between transformed cells. 91,127 Thus, Cas appears to act as a switch between intercellular communication and tumor cell migration downstream of Src kinase activity.…”

Section: Contact Normalizationmentioning

confidence: 99%

“…Pdpn associates with ezrin and regulates the activities of Rho GTPases to promote filopodia formation, cell motility, and metastasis. [152][153][154] Pdpn expression is induced by tumor promoters, including TPA, RAS, and Src, 127,155,156 and enhances transformed cell motility and invasion. 152,157 PDPN is predominantly found at the invasive front of many tumors, which is consistent with its role in promoting malignant invasion.…”

Section: Src and Downstream Chemotherapeutic Targetsmentioning

confidence: 99%

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Src Points the Way to Biomarkers and Chemotherapeutic Targets

Krishnan¹,

Miller

Goldberg³

2012

Genes & Cancer

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The role of Src in tumorigenesis has been extensively studied since the work of Peyton Rous over a hundred years ago. Src is a non-receptor tyrosine kinase that plays key roles in signaling pathways controlling tumor cell growth and migration. Src regulates the activities of numerous molecules to induce cell transformation. However, transformed cells do not always migrate and realize their tumorigenic potential. They can be normalized by surrounding nontransformed cells by a process called contact normalization. Tumor cells need to override contact normalization to become malignant or metastatic. In this review, we discuss the role of Src in cell migration and contact normalization, with emphasis on Cas and Abl pathways. This paradigm illuminates several chemotherapeutic targets and may lead to the identification of new biomarkers and the development of effective anticancer treatments.

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Independent effects of Src kinase and podoplanin on anchorage independent cell growth and migration

Retzbach

Sheehan

Krishnan

et al. 2022

Molecular Carcinogenesis

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The Src tyrosine kinase is a strong tumor promotor. Over a century of research has elucidated fundamental mechanisms that drive its oncogenic potential. Src phosphorylates effector proteins to promote hallmarks of tumor progression. For example, Src associates with the Cas focal adhesion adaptor protein to promote anchorage independent cell growth. In addition, Src phosphorylates Cas to induce Pdpn expression to promote cell migration. Pdpn is a transmembrane receptor that can independently increase cell migration in the absence of oncogenic Src kinase activity. However, to our knowledge, effects of Src kinase activity on anchorage independent cell growth and migration have not been examined in the absence of Pdpn expression. Here, we analyzed the effects of an inducible Src kinase construct in knockout cells with and without exogenous Pdpn expression on cell morphology migration and anchorage independent growth. We report that Src promoted anchorage independent cell growth in the absence of Pdpn expression. In contrast, Src was not able to promote cell migration in the absence of Pdpn expression. In addition, continued Src kinase activity was required for cells to assume a transformed morphology since cells reverted to a nontransformed morphology upon cessation of Src kinase activity. We also used phosphoproteomic analysis to identify 28 proteins that are phosphorylated in Src transformed cells in a Pdpn dependent manner. Taken together, these data indicate that Src utilizes Pdpn to promote transformed cell growth and motility in complementary, but parallel, as opposed to serial, pathways.

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Src Induces Podoplanin Expression to Promote Cell Migration

Cited by 52 publications

References 36 publications

Serines in the Intracellular Tail of Podoplanin (PDPN) Regulate Cell Motility

Serines in the Intracellular Tail of Podoplanin (PDPN) Regulate Cell Motility

Src Points the Way to Biomarkers and Chemotherapeutic Targets

Independent effects of Src kinase and podoplanin on anchorage independent cell growth and migration

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