Ror2 signaling regulated by differential Wnt proteins determines pathological fate of muscle mesenchymal progenitors.

Skeletal muscle mesenchymal progenitors (MPs) play a critical role in supporting muscle regeneration. However, under pathological conditions, they contribute to intramuscular adipose tissue accumulation, involved in muscle diseases, including muscular dystrophy and sarcopenia, age-related muscular atrophy. How MP fate is determined in these different contexts remains unelucidated.

Role of the Ror family receptors in Wnt5a signaling.

Ror-family receptors, Ror1 and Ror2, are type I transmembrane proteins that possess an extracellular cysteine-rich domain, which is conserved throughout the Frizzled-family receptors and is a binding site for Wnt ligands. Both Ror1 and Ror2 function primarily as receptors or co-receptors for Wnt5a to activate the β-catenin-independent, non-canonical Wnt signaling, thereby regulating cell polarity, migration, proliferation, and differentiation depending on the context. Ror1 and Ror2 are expressed highly in many tissues during embryogenesis but minimally or scarcely in adult tissues, with some exceptions.

Rho family small GTPase Rif regulates Wnt5a-Ror1-Dvl2 signaling and promotes lung adenocarcinoma progression.

Rho in filopodia (Rif), a member of the Rho family of small GTPases, induces filopodia formation primarily on the dorsal surface of cells; however, its function remains largely unclear. Here, we show that Rif interacts with Ror1, a receptor for Wnt5a that can also induce dorsal filopodia. Our immunohistochemical analysis revealed a high frequency of coexpression of Ror1 and Rif in lung adenocarcinoma.

Expression of Ferredoxin1 in cisplatin‑resistant ovarian cancer cells confers their resistance against ferroptosis induced by cisplatin.

Ovarian cancer (OC) is a refractory cancer that shows recurrence due to the acquisition of resistance to anticancer drugs, including cisplatin. However, the molecular mechanism underlying the acquisition of cisplatin resistance by cancer cells remains largely unknown. In the present study, two sets of ovarian endometrioid carcinoma cell lines were used: The parental A2780 cell line, the OVK18 cell line, and their derived cisplatin‑resistant cells.

Molecular mechanisms underlying the promotion of wound repair by coenzyme Q10: PI3K/Akt signal activation via alterations to cell membrane domains.

Coenzyme Q10 (CoQ10) promotes wound healing and . However, the molecular mechanisms underlying the promoting effects of CoQ10 on wound repair remain unknown. In the present study, we investigated the molecular mechanisms through which CoQ10 induces wound repair using a cellular wound-healing model.

The Ror-Family Receptors in Development, Tissue Regeneration and Age-Related Disease.

The Ror-family proteins, Ror1 and Ror2, act as receptors or co-receptors for Wnt5a and its related Wnt proteins to activate non-canonical Wnt signaling. Ror1 and/or Ror2-mediated signaling plays essential roles in regulating cell polarity, migration, proliferation and differentiation during developmental morphogenesis, tissue-/organo-genesis and regeneration of adult tissues following injury. Ror1 and Ror2 are expressed abundantly in developing tissues in an overlapping, yet distinct manner, and their expression in adult tissues is restricted to specific cell types such as tissue stem/progenitor cells.

Autonomous and intercellular chemokine signaling elicited from mesenchymal stem cells regulates migration of undifferentiated gastric cancer cells.

Accumulating evidence demonstrates that bone marrow (BM)-derived mesenchymal stem cells (MSCs) play critical roles in regulating progression of various types of cancer. We have previously shown that Wnt5a-Ror2 signaling in MSCs induces expression of CXCL16, and that CXCL16 secreted from MSCs then binds to its cognate receptor CXCR6 on the surface of an undifferentiated gastric cancer cell line MKN45 cells, eventually leading to proliferation and migration of MKN45 cells. However, it remains unclear about a possible involvement of another (other) cytokine(s) in regulating progression of gastric cancer.

Characterization of morphological alterations in micropapillary adenocarcinoma of the lung using an established cell line.

Micropapillary adenocarcinoma of the lung is a type of cancer associated with a poor prognosis and is characterized by the presence of tumor cells with a ring‑like glandular structure floating within alveolar spaces. In the present study, the association between its morphological, biochemical and immunohistochemical characteristics, and malignancy was investigated using the KU‑Lu‑MPPt3 cell line established from a patient with MIP adenocarcinoma. Two subpopulations of KU‑Lu‑MPPt3 cells, namely adhesive (AD) and clumpy and suspended (CS) cells, were prepared and subjected to DNA microarray, reverse transcription‑quantitative PCR, western blot and immunostaining analyses.

Oncogenic E6 and/or E7 proteins drive proliferation and invasion of human papilloma virus‑positive head and neck squamous cell cancer through upregulation of Ror2 expression.

Ror2 (receptor tyrosine kinase like orphan receptor 2) is highly expressed in various types of cancers; in the majority of these cancers, Ror2 expression is associated with more aggressive disease states. Recently, it has been reported that Ror2 is highly expressed in human papilloma virus (HPV)‑positive head and neck squamous cell cancer (HNSCC) cell lines, presumably indicating that Ror2 plays a critical role in HPV‑related cancers. However, the function of Ror2 in HPV‑positive HNSCC is currently unknown.

Role of noncanonical Wnt ligands and Ror-family receptor tyrosine kinases in the development, regeneration, and diseases of the musculoskeletal system.

The Ror-family receptor tyrosine kinases (RTKs), consisting of Ror1 and Ror2, play crucial roles in morphogenesis and formation of various tissues/organs, including the bones and skeletal muscles, the so-called musculoskeletal system, during embryonic development, by acting as receptors or coreceptors for a noncanonical Wnt protein Wnt5a. Furthermore, several lines of evidence have indicated that Ror1 and/or Ror2 play critical roles in the regeneration and maintenance of the musculoskeletal system in adults. Considering the anatomical and functional relationship between the skeleton and skeletal muscles, their structural and functional association might be tightly regulated during their embryonic development, development after birth, and their regeneration after injury in adults.

The Ror1 receptor tyrosine kinase plays a critical role in regulating satellite cell proliferation during regeneration of injured muscle.

The Ror family receptor tyrosine kinases, Ror1 and Ror2, play important roles in regulating developmental morphogenesis and tissue- and organogenesis, but their roles in tissue regeneration in adult animals remain largely unknown. In this study, we examined the expression and function of Ror1 and Ror2 during skeletal muscle regeneration. Using an skeletal muscle injury model, we show that expression of Ror1 and Ror2 in skeletal muscles is induced transiently by the inflammatory cytokines, TNF-α and IL-1β, after injury and that inhibition of TNF-α and IL-1β by neutralizing antibodies suppresses expression of and in injured muscles.

Ror2 signaling regulates Golgi structure and transport through IFT20 for tumor invasiveness.

Signaling through the Ror2 receptor tyrosine kinase promotes invadopodia formation for tumor invasion. Here, we identify intraflagellar transport 20 (IFT20) as a new target of this signaling in tumors that lack primary cilia, and find that IFT20 mediates the ability of Ror2 signaling to induce the invasiveness of these tumors. We also find that IFT20 regulates the nucleation of Golgi-derived microtubules by affecting the GM130-AKAP450 complex, which promotes Golgi ribbon formation in achieving polarized secretion for cell migration and invasion.