Rare Diseases Symptoms Automatic Extraction

Podocalyxin-like 1 promotes invadopodia formation and metastasis through activation of Rac1/Cdc42/cortactin signaling in breast cancer cells.

[wiskott-aldrich syndrome]

Metastatic disease is the leading cause of cancer mortality. Identifying biomarkers and regulatory mechanisms is important toward developing diagnostic and therapeutic tools against metastatic cancer. In this study, we demonstrated that podocalyxin-like 1 (PODXL) is overexpressed in breast tumor cells and increased in lymph node metastatic cancer. Mechanistically, we found that the expression of PODXL was associated with cell motility and invasiveness. Suppression of PODXL in MDA-MB-231 cells reduced lamellipodia formation and focal adhesion kinase (FAK) and paxillin phosphorylation. PODXL knockdown reduced the formation of invadopodia, such as inhibiting the colocalization of F-actin with cortactin and suppressing phosphorylation of cortactin and neural Wiskott-Aldrich syndrome protein. Conversely, overexpression of PODXL in MCF7 cells induced F-actin/cortactin colocalization and enhanced invadopodia formation and activation. Invadopodia activity and tumor invasion in PODXL-knockdown cells are similar to that in cortactin-knockdown cells. We further found that the DTHL motif in PODXL is crucial for regulating cortactin phosphorylation and Rac1/Cdc42 activation. Inhibition of Rac1/Cdc42 impeded PODXL-mediated cortactin activation and FAK and paxillin phosphorylation. Moreover, inhibition of PODXL in MDA-MB-231 cells significantly suppressed tumor colonization in the lungs and distant metastases, similar to those in cortactin-knockdown cells. These findings show that overexpression of PODXL enhanced invadopodia formation and tumor metastasis by inducing Rac1/Cdc42/cortactin signaling network.

Diseases presenting "cancer" symptom

  • achondroplasia
  • acute rheumatic fever
  • adrenal incidentaloma
  • alpha-thalassemia
  • benign recurrent intrahepatic cholestasis
  • cadasil
  • canavan disease
  • carcinoma of the gallbladder
  • cholangiocarcinoma
  • coats disease
  • congenital adrenal hyperplasia
  • congenital diaphragmatic hernia
  • cowden syndrome
  • cushing syndrome
  • cutaneous mastocytosis
  • dedifferentiated liposarcoma
  • dystrophic epidermolysis bullosa
  • epidermolysis bullosa simplex
  • erdheim-chester disease
  • erythropoietic protoporphyria
  • esophageal adenocarcinoma
  • esophageal carcinoma
  • esophageal squamous cell carcinoma
  • familial hypocalciuric hypercalcemia
  • familial mediterranean fever
  • gm1 gangliosidosis
  • heparin-induced thrombocytopenia
  • hereditary cerebral hemorrhage with amyloidosis
  • hirschsprung disease
  • hodgkin lymphoma, classical
  • inclusion body myositis
  • junctional epidermolysis bullosa
  • kabuki syndrome
  • kallmann syndrome
  • kindler syndrome
  • lamellar ichthyosis
  • liposarcoma
  • locked-in syndrome
  • lymphangioleiomyomatosis
  • monosomy 21
  • neuralgic amyotrophy
  • oculocutaneous albinism
  • oligodontia
  • oral submucous fibrosis
  • papillon-lefèvre syndrome
  • pendred syndrome
  • pleomorphic liposarcoma
  • primary effusion lymphoma
  • proteus syndrome
  • pyomyositis
  • pyruvate dehydrogenase deficiency
  • severe combined immunodeficiency
  • sneddon syndrome
  • systemic capillary leak syndrome
  • triple a syndrome
  • von hippel-lindau disease
  • waldenström macroglobulinemia
  • well-differentiated liposarcoma
  • werner syndrome
  • wiskott-aldrich syndrome
  • wolf-hirschhorn syndrome
  • x-linked adrenoleukodystrophy

This symptom has already been validated