Hedgehog Signaling in Lung Cancer: From Oncogenesis to Cancer Treatment Resistance

Leprieur, Étienne Giroux; Costantini, Adrien; Ding, Vivianne W.; He, Biao

doi:10.3390/ijms19092835

Cited by 86 publications

(86 citation statements)

References 162 publications

(198 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The non-canonical cascade exists to elicit various cellular responses, especially in cancers [36]. One of the mechanisms of non-canonical SHH signaling involves the activation of Gli transcriptional factors independently of SHH, Ptch and SMO.…”

Section: Shh Signaling Pathwaymentioning

confidence: 99%

“…Beside its critical role in multiple developmental processes of organs and tissues, such as bone (see above), the Hedgehog-Gli signaling pathway is aberrantly activated in several human cancers [35,36,[114][115][116][117][118].…”

Section: Shh Signaling In Os Et Esmentioning

confidence: 99%

“…The SHH pathway can be also activated without mutations of the genes involved in the SHH cascade, mainly through a paracrine effect of SHH and, thus, on the canonical cascade [35,36,[115][116][117][118]. Schematically, Gli transcriptional factor may act at different steps of tumorigenesis [118].…”

Section: Shh Signaling In Os Et Esmentioning

confidence: 99%

See 2 more Smart Citations

SHH Signaling Pathway Drives Pediatric Bone Sarcoma Progression

Lezot¹,

Corre²,

Morice³

et al. 2020

Cells

View full text Add to dashboard Cite

Primary bone tumors can be divided into two classes, benign and malignant. Among the latter group, osteosarcoma and Ewing sarcoma are the most prevalent malignant primary bone tumors in children and adolescents. Despite intensive efforts to improve treatments, almost 40% of patients succumb to the disease. Specifically, the clinical outcome for metastatic osteosarcoma or Ewing sarcoma remains poor; less than 30% of patients who present metastases will survive 5 years after initial diagnosis. One common and specific point of these bone tumors is their ability to deregulate bone homeostasis and remodeling and divert them to their benefit. Over the past years, considerable interest in the Sonic Hedgehog (SHH) pathway has taken place within the cancer research community. The activation of this SHH cascade can be done through different ways and, schematically, two pathways can be described, the canonical and the non-canonical. This review discusses the current knowledge about the involvement of the SHH signaling pathway in skeletal development, pediatric bone sarcoma progression and the related therapeutic options that may be possible for these tumors.

show abstract

Section: Shh Signaling Pathwaymentioning

confidence: 99%

Section: Shh Signaling In Os Et Esmentioning

confidence: 99%

See 1 more Smart Citation

SHH Signaling Pathway Drives Pediatric Bone Sarcoma Progression

Lezot¹,

Corre²,

Morice³

et al. 2020

Cells

View full text Add to dashboard Cite

show abstract

“…Although Giroux‐Leprieur et al . reported about the association of cancer stemness and drug resistance in terms of Hedgehog signaling, there are few previous reports about the correlation of cancer stemness and histological transformation.…”

mentioning

confidence: 99%

“…In this case we focus on the cancer stemness as the mechanisms of TKI resistance, because in our previous study we demonstrated the drug-tolerant clones were consisted of cancer stem cells and senescent cells. 4 Although Giroux-Leprieur et al reported about the association of cancer stemness and drug resistance in terms of Hedgehog signaling, 5 there are few previous reports about the correlation of cancer stemness and histological transformation.…”

mentioning

confidence: 99%

Overexpression of CD 133 and BCL‐2 in non‐small cell lung cancer with neuroendocrine differentiation after transformation in ALK rearrangement‐positive adenocarcinoma

Koyama

Katsurada

Jimbo³

et al. 2019

Pathology International

View full text Add to dashboard Cite

Transformation to small cell lung cancer is one phenomenon of acquired resistance to anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors in ALK rearrangement‐positive non‐small cell lung cancer (NSCLC). Few case reports have focused on other types of histological transformation. We report a case of transformation of ALK rearrangement‐positive adenocarcinoma to NSCLC with neuroendocrine differentiation during alectinib therapy. A 36‐year‐old woman presented with a tumor in the left lower lobe and bone metastases. She was diagnosed with ALK rearrangement‐positive adenocarcinoma by histopathology of the primary tumor. Alectinib had been effective for 8 months before new lesions appeared. Histopathological re‐examination of a recurrent tumor revealed poorly differentiated carcinoma with insulinoma‐associated protein 1 (INSM1) expression, which remained ALK‐positive. Expression of CD133, BCL‐2, and SOX2 was positive in comparison to the initial tumor. Expression of SOX2 became more strongly positive than it was before treatment. The immunohistochemical findings of these markers associated with cancer stem‐like cells and/or neuroendocrine differentiation suggest that cancer stem cells play a role in the mechanisms of histological transformation and acquired resistance of ALK rearrangement‐positive cancer. To our knowledge, this is the first report to suggest an association between cancer stem‐like cells and histological transformation in ALK rearrangement‐positive lung cancer.

show abstract

Exosomal Sonic Hedgehog derived from cancer‐associated fibroblasts promotes proliferation and migration of esophageal squamous cell carcinoma

Zhao

Guo

et al. 2020

Cancer Medicine

View full text Add to dashboard Cite

Esophageal squamous cell carcinoma (ESCC) is one of the most common and aggressive malignancies in China. Cancer‐associated fibroblasts (CAFs) can actively communicate with and stimulate tumor cells, thereby contributing to the development and progression of tumors. Yet, whether CAFs‐derived exosomes have a role in the progression of ESCC is largely unknown. Here, we find that Sonic Hedgehog (SHH) is highly expressed in CAFs lysis solution, conditioned medium of cultured CAFs (CAF‐CM) and CAFs‐derived exosomes, and esophageal cancer cell lines educated by CAF‐CM and CAFs‐derived exosomes can improve their growth and migration abilities in vitro and in vivo. Besides, those effects can be partly neutralized by cyclopamine, inhibitor of the Hedgehog signaling pathway. Thus, our research elucidates the crucial role of CAFs‐derived exosomes in the growth and progression of ESCC, and may open up new avenues in the treatment of ESCC.

show abstract

Hedgehog Signaling in Lung Cancer: From Oncogenesis to Cancer Treatment Resistance

Cited by 86 publications

References 162 publications

SHH Signaling Pathway Drives Pediatric Bone Sarcoma Progression

SHH Signaling Pathway Drives Pediatric Bone Sarcoma Progression

Overexpression of CD 133 and BCL‐2 in non‐small cell lung cancer with neuroendocrine differentiation after transformation in ALK rearrangement‐positive adenocarcinoma

Exosomal Sonic Hedgehog derived from cancer‐associated fibroblasts promotes proliferation and migration of esophageal squamous cell carcinoma

Contact Info

Product

Resources

About