A new research paper was published in Oncotarget's Volume 14 on March 24, 2023, entitled, “Downregulation of angulin-1/LSR induces malignancy via upregulation of EGF-dependent claudin-2 and TGF-β-dependent cell metabolism in human lung adenocarcinoma A549 cells.”

Abnormal expression of bicellular tight junction claudins, including claudin-2 are observed during carcinogenesis in human lung adenocarcinoma. However, little is known about the role of tricellular tight junction molecule angulin-1/lipolysis-stimulated lipoprotein receptor (LSR). 

In the present study, researchers Wataru Arai, Takumi Konno, Takayuki Kohno, Yuki Kodera, Mitsuhiro Tsujiwaki, Yuma Shindo, Hirofumi Chiba, Masahiro Miyajima, Yuji Sakuma, Atsushi Watanabe, and Takashi Kojima from Sapporo Medical University School of Medicine examined expression of claudin-2 in the lung adenocarcinoma tissues and found it was higher than in normal lung tissues, while angulin-1/LSR was poorly or faintly expressed. 

“We investigated how loss of angulin-1/LSR affects the malignancy of lung adenocarcinoma cell line A549 and normal human lung epithelial (HLE) cells.” 

The researchers found that the EGF receptor tyrosine kinase inhibitor AG1478 prevented the increase of claudin-2 expression induced by EGF in A549 cells. Knockdown of LSR induced expression of claudin-2 at the protein and mRNA levels and AG1478 prevented the upregulation of claudin-2 in A549 cells. Knockdown of LSR induced cell proliferation, cell migration and cell metabolism in A549 cells. Knockdown of claudin-2 inhibited the cell proliferation but did not affect the cell migration or cell metabolism of A549 cells. 

The TGF-β type I receptor inhibitor EW-7197 prevented the decrease of LSR and claudin-2 induced by TGF-β1 in A549 cells and 2D culture of normal HLE cells. EW-7197 prevented the increase of cell migration and cell metabolism induced by TGF-β1 in A549 cells. EW-7197 prevented the increase of epithelial permeability of FITC-4kD dextran induced by TGF-β1 in 2.5D culture of normal HLE cells. In conclusion, downregulation of angulin-1/LSR induces malignancy via EGF-dependent claudin-2 and TGF-β-dependent cell metabolism in human lung adenocarcinoma.

“In conclusion, AG1478 and EW-7197 demonstrated potent in vitro anti-lung adenocarcinoma therapeutic activities via LSR/CLDN-2 and the cell metabolism. The use of both AG1478 and EW-7197 may provide a clinical therapeutic approach for lung adenocarcinoma caused by loss of angulin-1/LSR.”

Full research paper: DOI: https://doi.org/10.18632/oncotarget.27728 

Correspondence to: Takashi Kojima - ktakashi@sapmed.ac.jp 

Keywords: angulin-1/LSR, claudin-2, cell metabolism, malignancy, lung adenocarcinoma

About Oncotarget

Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed.

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Oncotarget

Downregulation of Angulin-1/LSR Induces Malignancy in Lung Adenocarcinoma

Welcome back to The Great Metal Debate podcast. Today we are talking about the fourth full-length studio album by the New York brutal tech death band Malignancy titled ...Discontinued, which was dropped on June 14th through Willowtip Records.

This is the band's first album in 12 years so this certainly calls for celebration. For a band that has been around since 1992, you would think that they would have much more albums in their discography but, I guess some bands like to really take the time with their craft.

Before diving into this new record track by track, I'm going point out a major similarity that I've always noticed about this band. Particularly with the vocalist Danny Nelson having a nearly identical sounding voice to Ross Dolan from Immolation. I had often wondered if Malignancy was a side project band, which would make a lot of sense seeing as how both bands are from Yonkers! The answer is no, Danny and Ross are two different people. However, Danny had done vocals for Mortal Decay's 2013 album The Blueprint For Blood Spatter.

When I looked up the names of the band members, I had to do a double take when I saw the bass player. At first I thought it said Alex Webster from Cannibal Corpse, but nope, the new bass player is Alex Weber. Haha, not Webster.

Coincidentally enough, guess where Cannibal Corpse originally started. You guessed it, New York. Except they formed in Buffalo. According to Metal-Archives, Alex Weber has played live for Defeated Sanity and Obscura. Guitarist Ron Kachnic has also been in Pyrexia, Demolition Hammer and Mortician! Mike Heller has been the drummer for multiple bands including System Divide which is Sven from Aborted's side project band. Despite not advertising as such, Malignancy IS a super group.

Kicking things off we have the first track titled "Existential Dread". As you listen to this album, you can feel Danny's lips press against the microphone as he delivers his powerful vocals. You can tell he definitely uses his diaphragm to produce such a monstrous tone. Watch a few live videos of them and you can witness for yourself Danny's commanding stage presence too.

"Purity of Purpose" was the first single released for this album about 2 months beforehand. I remembered as soon as I heard it, I immediately looked up the full-length release date and album title just to add it to my list. Judging from that track alone, I knew I had to review it.

The second single "Biological Absurdity" was uploaded a month later and it of course blew me away. Both of these songs were aired on YouTube as official tracks but we haven't been treated to a music video yet.

I have found myself jamming this album front to back since its release a little over a week ago and I gotta say, I'm impressed! I mean, Malignancy never disappoints. This album is absolutely killer and one of the finest examples of your standard death metal.

Bad ass death metal albums without an overly unique pizazz quality about them are still more than capable of getting a good rating out of me. This is definitely one of the better straight forward death metal albums I've heard in 2024 so far. With that being said, I'm feeling a nice 8/10 rating.

Malignancy has been kickin around in the underground scene since I was a 1-year-old. They've gone through a few line-up changes here and there but have held strong as a band for the past three decades. Their popularity may not be up on the same level as many other bands but they deserve a lot of credit, respect and most of all support.

You can buy their merch ... at pretty much any online metal merch outlet. The most obvious choice would be bandcamp, but they also have merch at primitiverecordings.com, hellsheadbangers.com and indiemerch.com. Of course, if you get lucky enough to see them live; they definitely have a merch table and I hear that they are usually at their stand before and after a show. So don't be shy, go say hi and if nothing else, throw them a few bucks in their tip jar.

The Great Metal Debate

Metal Debate Album Review - Discontinued (Malignancy)

In this interview Xander is joined by the guys in Malignancy before their show at The Brass Mug in Tampa!

Excerpts from the Malignancy track "Existential Dread" (2024) used with permission from the artist.


Check out Malignancy's music at  https://www.youtube.com/@MalignancyNY 

Purchase music and merchandise from Malignancy at https://malignancy.bandcamp.com/music 


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Metal Debate Interview - Malignancy (02-22-2025)

Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form and then quickly released to Pubmed.

Oncotarget is now indexed by MEDLINE, PubMed and PMC/PubMed.

Read about the Oncotarget Scientific Integrity Process: https://www.oncotarget.com/scientific_integrity/

Podcast where Gomthog and co-hosts engage in lively debates on heavy metal music as well as interviewing artists and reviewing albums.  Occasional explicit language.

New tracks tagged #Malignancy